請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7510
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林慧玲 | zh_TW |
dc.contributor.advisor | Fe-Lin Lin Wu | en |
dc.contributor.author | 温俊銘 | zh_TW |
dc.contributor.author | Chun-Ming Wen | en |
dc.date.accessioned | 2021-05-19T17:45:15Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-11 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 1. Johnson HJS KS. Solid-organ transplantation. In: DiPiro JTT, R.L.; Yee, G.C., ed. Pharmacotherapy. 6 ed. New York: McGraw-Hill; 2005.
2. Bowman LJ, Brennan DC. The role of tacrolimus in renal transplantation. Expert opinion on pharmacotherapy 2008;9:635-43. 3. Kershner RP, Fitzsimmons WE. Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation. Transplantation 1996;62:920-6. 4. Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ. An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation 1996;62:900-5. 5. Mourad M, Wallemacq P, De Meyer M, et al. Biotransformation enzymes and drug transporters pharmacogenetics in relation to immunosuppressive drugs: impact on pharmacokinetics and clinical outcome. Transplantation 2008;85:S19-24. 6. Coto E, Tavira B. Pharmacogenetics of calcineurin inhibitors in renal transplantation. Transplantation 2009;88:S62-7. 7. Venkataramanan R, Swaminathan A, Prasad T, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 1995;29:404-30. 8. Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs 2003;63:1247-97. 9. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. The New England journal of medicine 2007;357:2562-75. 10. Oberbauer R. Improved renal function in de novo renal transplant patients on sirolimus maintenance therapy following discontinuation of cyclosporine. Ther Drug Monit 2005;27:7-9. 11. Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB. Strategies to improve long-term outcomes after renal transplantation. The New England journal of medicine 2002;346:580-90. 12. Borobia AM, Romero I, Jimenez C, et al. Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection. Ther Drug Monit 2009;31:436-42. 13. O'Seaghdha CM, McQuillan R, Moran AM, et al. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection. Clin Transplant 2009;23:462-8. 14. Han SS, Kim DH, Lee SM, et al. Pharmacokinetics of tacrolimus according to body composition in recipients of kidney transplants. Kidney research and clinical practice 2012;31:157-62. 15. Quteineh L, Verstuyft C, Furlan V, et al. Influence of CYP3A5 genetic polymorphism on tacrolimus daily dose requirements and acute rejection in renal graft recipients. Basic & clinical pharmacology & toxicology 2008;103:546-52. 16. Staatz CE, Goodman LK, Tett SE. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clin Pharmacokinet 2010;49:141-75. 17. Renders L, Frisman M, Ufer M, et al. CYP3A5 genotype markedly influences the pharmacokinetics of tacrolimus and sirolimus in kidney transplant recipients. Clin Pharmacol Ther 2007;81:228-34. 18. MacPhee IA, Fredericks S, Tai T, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant 2004;4:914-9. 19. Zhang X, Liu ZH, Zheng JM, et al. Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation. Clin Transplant 2005;19:638-43. 20. Kim IW, Moon YJ, Ji E, et al. Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients. Eur J Clin Pharmacol 2012;68:657-69. 21. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 2004;43:623-53. 22. Floren LC, Bekersky I, Benet LZ, et al. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Pharmacol Ther 1997;62:41-9. 23. Zhao W, Elie V, Roussey G, et al. Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients. Clin Pharmacol Ther 2009;86:609-18. 24. Antignac M, Barrou B, Farinotti R, Lechat P, Urien S. Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patients. British journal of clinical pharmacology 2007;64:750-7. 25. Staatz CE, Willis C, Taylor PJ, Tett SE. Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clin Pharmacol Ther 2002;72:660-9. 26. Press RR, de Fijter JW, Guchelaar HJ. Individualizing calcineurin inhibitor therapy in renal transplantation--current limitations and perspectives. Current pharmaceutical design 2010;16:176-86. 27. Ware N, MacPhee IA. Current progress in pharmacogenetics and individualized immunosuppressive drug dosing in organ transplantation. Current opinion in molecular therapeutics 2010;12:270-83. 28. Velickovic-Radovanovic R, Mikov M, Paunovic G, et al. Gender differences in pharmacokinetics of tacrolimus and their clinical significance in kidney transplant recipients. Gender medicine 2011;8:23-31. 29. Masuda S, Inui K. An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacology & therapeutics 2006;112:184-98. 30. Chen YH, Zheng KL, Chen LZ, et al. Clinical pharmacokinetics of tacrolimus after the first oral administration in combination with mycophenolate mofetil and prednisone in Chinese renal transplant recipients. Transplant Proc 2005;37:4246-50. 31. Dai Y, Hebert MF, Isoherranen N, et al. Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug Metab Dispos 2006;34:836-47. 32. Morrissey PE, Gohh R, Shaffer D, et al. Correlation of clinical outcomes after tacrolimus conversion for resistant kidney rejection or cyclosporine toxicity with pathologic staging by the Banff criteria. Transplantation 1997;63:845-8. 33. Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 2004;4:1289-95. 34. Mayer AD, Dmitrewski J, Squifflet JP, et al. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 1997;64:436-43. 35. Goto T, Kino T, Hatanaka H, et al. Discovery of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987;19:4-8. 36. Kino T, Hatanaka H, Hashimoto M, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. The Journal of antibiotics 1987;40:1249-55. 37. Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A. FK 506 for liver, kidney, and pancreas transplantation. Lancet (London, England) 1989;2:1000-4. 38. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet (London, England) 1994;344:423-8. 39. A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. The New England journal of medicine 1994;331:1110-5. 40. Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation 1997;63:977-83. 41. Klintmalm GB, Goldstein R, Gonwa T, et al. Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group. Transplant Proc 1993;25:679-88. 42. Spencer CM, Goa KL, Gillis JC. Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 1997;54:925-75. 43. Peters DH, Fitton A, Plosker GL, Faulds D. Tacrolimus. A review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs 1993;46:746-94. 44. Plosker GL, Foster RH. Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs 2000;59:323-89. 45. Kapp A, Allen BR, Reitamo S. Atopic dermatitis management with tacrolimus ointment (Protopic). The Journal of dermatological treatment 2003;14:5-16. 46. Russell JJ. Topical tacrolimus: a new therapy for atopic dermatitis. American family physician 2002;66:1899-902. 47. Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant 2018;18 Suppl 1:18-113. 48. Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998;92:2303-14. 49. Jindal RM, Dubernard JM. Towards a specific immunosuppression for pancreas and islet grafts. Clin Transplant 2000;14:242-5. 50. Stratta RJ. Immunosuppression in pancreas transplantation: progress, problems and perspective. Transplant immunology 1998;6:69-77. 51. Klein A. Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine. The US Multicenter FK506 Liver Study Group. Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 1999;5:502-8. 52. Laskow DA, Neylan JF, 3rd, Shapiro RS, Pirsch JD, Vergne-Marini PJ, Tomlanovich SJ. The role of tacrolimus in adult kidney transplantation: a review. Clin Transplant 1998;12:489-503. 53. Dubinsky MC, Seidman EG. Novel immunosuppressive therapies for intestinal and hepatic diseases. Current opinion in pediatrics 1999;11:390-5. 54. Singer NG, McCune WJ. Update on immunosuppressive therapy. Current opinion in rheumatology 1998;10:169-73. 55. Schiff J, Cole E, Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clinical journal of the American Society of Nephrology : CJASN 2007;2:374-84. 56. de Jonge H, Naesens M, Kuypers DR. New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit 2009;31:416-35. 57. Jusko WJ, Piekoszewski W, Klintmalm GB, et al. Pharmacokinetics of tacrolimus in liver transplant patients. Clin Pharmacol Ther 1995;57:281-90. 58. Regazzi MB, Rinaldi M, Molinaro M, et al. Clinical pharmacokinetics of tacrolimus in heart transplant recipients. Ther Drug Monit 1999;21:2-7. 59. Backman L, Levy MF, Klintmalm G. Whole-blood and plasma levels of FK 506 after liver transplantation: results from the US Multicenter Trial. FK506 Multicenter Study Group. Transplant Proc 1995;27:1124. 60. Winkler M, Ringe B, Jost U, Gubernatis G, Pichlmayr R. Plasma level-guided low-dose FK 506 therapy in patients with early liver dysfunction after liver transplantation. Transplant Proc 1993;25:2688-90. 61. Schwartz M, Holst B, Facklam D, Buell D. FK 506 in liver transplantation: correlation of whole blood levels with efficacy and toxicity. The US Multicenter FK 506 Dose Optimization. Transplant Proc 1995;27:1107. 62. Townsend CM. Sabiston Textbook of Surgery. 19 ed. United States: Saunders; 2012. 63. Krensky AMV FB, W.M. Immunosuppressants, tolerogens, and immunostimulants. In: Brunton LLL, J.S.; Parker, K.L., ed. The pharmacological basis of therapeutics. 11 ed. New York: McGraw-Hill; 2006. 64. Tsai MK, Yang CY, Lee CY, Yeh CC, Hu RH, Lee PH. De novo malignancy is associated with renal transplant tourism. Kidney Int 2011;79:908-13. 65. Andres A. Cancer incidence after immunosuppressive treatment following kidney transplantation. Critical reviews in oncology/hematology 2005;56:71-85. 66. Kauffman HM, Cherikh WS, McBride MA, Cheng Y, Hanto DW. Post-transplant de novo malignancies in renal transplant recipients: the past and present. Transpl Int 2006;19:607-20. 67. Johnson HJS, K.S. Solid-organ transplantation. In: DiPiro JTT, R.L.; Yee, G.C., ed. Pharmacotherapy. 6 ed. New York: McGraw-Hill; 2005:1613-43. 68. Krensky AMV, F.; Bennett, W.M. Immunosuppressants, tolerogens, and immunostimulants. In: Brunton LLL, J.S.; Parker, K.L., ed. The pharmacological basis of therapeutics. 11 ed. New York: McGraw-Hill; 2006:1405-65. 69. Pons JA, Ramirez P, Revilla-Nuin B, et al. Immunosuppression withdrawal improves long-term metabolic parameters, cardiovascular risk factors and renal function in liver transplant patients. Clinical transplantation 2009;23:329-36. 70. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. The New England journal of medicine 2003;349:931-40. 71. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clinical journal of the American Society of Nephrology : CJASN 2009;4:481-508. 72. Murray GI, McFadyen MC, Mitchell RT, Cheung YL, Kerr AC, Melvin WT. Cytochrome P450 CYP3A in human renal cell cancer. British journal of cancer 1999;79:1836-42. 73. Koch I, Weil R, Wolbold R, et al. Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA. Drug Metab Dispos 2002;30:1108-14. 74. Webster A, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. The Cochrane database of systematic reviews 2005:Cd003961. 75. Yates CJ, Fourlanos S, Hjelmesaeth J, Colman PG, Cohney SJ. New-onset diabetes after kidney transplantation-changes and challenges. Am J Transplant 2012;12:820-8. 76. Bechstein WO. Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transpl Int 2000;13:313-26. 77. Bottiger Y, Brattstrom C, Tyden G, Sawe J, Groth CG. Tacrolimus whole blood concentrations correlate closely to side-effects in renal transplant recipients. Br J Clin Pharmacol 1999;48:445-8. 78. Cordon-Cardo C, O'Brien JP, Casals D, et al. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proceedings of the National Academy of Sciences of the United States of America 1989;86:695-8. 79. Yanagimachi M, Naruto T, Tanoshima R, et al. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clin Transplant 2010;24:855-61. 80. Gervasini G, Garcia M, Macias RM, Cubero JJ, Caravaca F, Benitez J. Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation. Transpl Int 2012;25:471-80. 81. Hansten PDH, J.R. Drug interactions analysis and management 2007. St. Louis, Missouri: Wolters Kluwer; 2007. 82. Venkataramanan R, Jain A, Warty VS, et al. Pharmacokinetics of FK 506 in transplant patients. Transplant Proc 1991;23:2736-40. 83. Nagase K, Iwasaki K, Nozaki K, Noda K. Distribution and protein binding of FK506, a potent immunosuppressive macrolide lactone, in human blood and its uptake by erythrocytes. J Pharm Pharmacol 1994;46:113-7. 84. Mourad M, Wallemacq P, De Meyer M, et al. The influence of genetic polymorphisms of cytochrome P450 3A5 and ABCB1 on starting dose- and weight-standardized tacrolimus trough concentrations after kidney transplantation in relation to renal function. Clinical chemistry and laboratory medicine 2006;44:1192-8. 85. Undre NA, Schafer A. Factors affecting the pharmacokinetics of tacrolimus in the first year after renal transplantation. European Tacrolimus Multicentre Renal Study Group. Transplant Proc 1998;30:1261-3. 86. Kay JE, Sampare-Kwateng E, Geraghty F, Morgan GY. Uptake of FK 506 by lymphocytes and erythrocytes. Transplant Proc 1991;23:2760-2. 87. Klimecki WT, Futscher BW, Grogan TM, Dalton WS. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 1994;83:2451-8. 88. Kobayashi M, Tamura K, Katayama N, et al. FK 506 assay past and present--characteristics of FK 506 ELISA. Transplant Proc 1991;23:2725-9. 89. Piekoszewski W, Jusko WJ. Plasma protein binding of tacrolimus in humans. Journal of pharmaceutical sciences 1993;82:340-1. 90. Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001;40:283-95. 91. Hesselink DA, van Gelder T, van Schaik RH. The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immunosuppression? Pharmacogenomics 2005;6:323-37. 92. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993;268:6077-80. 93. Lampen A, Christians U, Guengerich FP, et al. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab Dispos 1995;23:1315-24. 94. Nakazawa Y, Chisuwa H, Ikegami T, et al. Relationship between in vivo FK506 clearance and in vitro 13-demethylation activity in living-related liver transplantation. Transplantation 1998;66:1089-93. 95. Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos 1992;20:753-61. 96. Vincent SH, Karanam BV, Painter SK, Chiu SH. In vitro metabolism of FK-506 in rat, rabbit, and human liver microsomes: identification of a major metabolite and of cytochrome P450 3A as the major enzymes responsible for its metabolism. Archives of biochemistry and biophysics 1992;294:454-60. 97. Press RR, Ploeger BA, den Hartigh J, et al. Explaining variability in tacrolimus pharmacokinetics to optimize early exposure in adult kidney transplant recipients. Ther Drug Monit 2009;31:187-97. 98. Bai JP, Lesko LJ, Burckart GJ. Understanding the genetic basis for adverse drug effects: the calcineurin inhibitors. Pharmacotherapy 2010;30:195-209. 99. Rosso Felipe C, de Sandes TV, Sampaio EL, Park SI, Silva HT, Jr., Medina Pestana JO. Clinical impact of polymorphisms of transport proteins and enzymes involved in the metabolism of immunosuppressive drugs. Transplant Proc 2009;41:1441-55. 100. Capron A, Mourad M, De Meyer M, et al. CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation. Pharmacogenomics 2010;11:703-14. 101. Kuypers DR, de Jonge H, Naesens M, Lerut E, Verbeke K, Vanrenterghem Y. CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther 2007;82:711-25. 102. Li D, Gui R, Li J, Huang Z, Nie X. Tacrolimus dosing in Chinese renal transplant patients is related to MDR1 gene C3435T polymorphisms. Transplant Proc 2006;38:2850-2. 103. Fredericks S, Moreton M, Reboux S, et al. Multidrug resistance gene-1 (MDR-1) haplotypes have a minor influence on tacrolimus dose requirements. Transplantation 2006;82:705-8. 104. Barry A, Levine M. A systematic review of the effect of CYP3A5 genotype on the apparent oral clearance of tacrolimus in renal transplant recipients. Ther Drug Monit 2010;32:708-14. 105. Iwasaki K. Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet 2007;22:328-35. 106. Wu MJ, Chang CH, Cheng CY, et al. Reduced variability of tacrolimus trough level in once-daily tacrolimus-based Taiwanese kidney transplant recipients with high-expressive genotype of cytochrome P450 3A5. Transplant Proc 2014;46:403-5. 107. Anglicheau D, Verstuyft C, Laurent-Puig P, et al. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J Am Soc Nephrol 2003;14:1889-96. 108. Tsuchiya N, Satoh S, Tada H, et al. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation 2004;78:1182-7. 109. Bekersky I, Dressler D, Mekki Q. Effect of time of meal consumption on bioavailability of a single oral 5 mg tacrolimus dose. J Clin Pharmacol 2001;41:289-97. 110. Kuypers DR, Claes K, Evenepoel P, et al. Time-related clinical determinants of long-term tacrolimus pharmacokinetics in combination therapy with mycophenolic acid and corticosteroids: a prospective study in one hundred de novo renal transplant recipients. Clin Pharmacokinet 2004;43:741-62. 111. Mourad M, Mourad G, Wallemacq P, et al. Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids. Transplantation 2005;80:977-84. 112. Marchesini G, Bua V, Brunori A, et al. Galactose elimination capacity and liver volume in aging man. Hepatology (Baltimore, Md) 1988;8:1079-83. 113. Woodhouse KW, Wynne HA. Age-related changes in liver size and hepatic blood flow. The influence on drug metabolism in the elderly. Clin Pharmacokinet 1988;15:287-94. 114. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OF. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology (Baltimore, Md) 1989;9:297-301. 115. Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997;61:331-9. 116. Ginsberg G, Hattis D, Russ A, Sonawane B. Pharmacokinetic and pharmacodynamic factors that can affect sensitivity to neurotoxic sequelae in elderly individuals. Environmental health perspectives 2005;113:1243-9. 117. Pichard L, Fabre I, Daujat M, Domergue J, Joyeux H, Maurel P. Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Molecular pharmacology 1992;41:1047-55. 118. Hustert E, Haberl M, Burk O, et al. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 2001;11:773-9. 119. Miura M, Satoh S, Kagaya H, et al. No impact of age on dose-adjusted pharmacokinetics of tacrolimus, mycophenolic acid and prednisolone 1 month after renal transplantation. Eur J Clin Pharmacol 2009;65:1047-53. 120. Jacobson PA, Schladt D, Oetting WS, et al. Lower calcineurin inhibitor doses in older compared to younger kidney transplant recipients yield similar troughs. Am J Transplant 2012;12:3326-36. 121. Gijsen V, Mital S, van Schaik RH, et al. Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2011;30:1352-9. 122. Kahan BD, Keown P, Levy GA, Johnston A. Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clinical therapeutics 2002;24:330-50; discussion 29. 123. Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet 2003;42:107-21. 124. Greenblatt DJ, von Moltke LL. Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. J Clin Pharmacol 2008;48:1350-5. 125. Wolbold R, Klein K, Burk O, et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology (Baltimore, Md) 2003;38:978-88. 126. Christiaans M, van Duijnhoven E, Beysens T, Undre N, Schafer A, van Hooff J. Effect of breakfast on the oral bioavailability of tacrolimus and changes in pharmacokinetics at different times posttransplant in renal transplant recipients. Transplant Proc 1998;30:1271-3. 127. Sewing KF. Pharmacokinetics, dosing principles, and blood level monitoring of FK506. Transplant Proc 1994;26:3267-9. 128. Han N, Yun HY, Hong JY, et al. Prediction of the tacrolimus population pharmacokinetic parameters according to CYP3A5 genotype and clinical factors using NONMEM in adult kidney transplant recipients. Eur J Clin Pharmacol 2013;69:53-63. 129. Antignac M, Hulot JS, Boleslawski E, et al. Population pharmacokinetics of tacrolimus in full liver transplant patients: modelling of the post-operative clearance. Eur J Clin Pharmacol 2005;61:409-16. 130. Fukatsu S, Yano I, Igarashi T, et al. Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation. Eur J Clin Pharmacol 2001;57:479-84. 131. Jain AB, Venkataramanan R, Cadoff E, et al. Effect of hepatic dysfunction and T tube clamping on FK 506 pharmacokinetics and trough concentrations. Transplant Proc 1990;22:57-9. 132. Winkler M, Ringe B, Rodeck B, et al. The use of plasma levels for FK 506 dosing in liver-grafted patients. Transplant international : official journal of the European Society for Organ Transplantation 1994;7:329-33. 133. Jain AB, Abu-Elmagd K, Abdallah H, et al. Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion. J Clin Pharmacol 1993;33:606-11. 134. Lee JY, Hahn HJ, Son IJ, et al. Factors affecting the apparent clearance of tacrolimus in Korean adult liver transplant recipients. Pharmacotherapy 2006;26:1069-77. 135. Hu RH, Lee PH, Tsai MK. Clinical influencing factors for daily dose, trough level, and relative clearance of tacrolimus in renal transplant recipients. Transplant Proc 2000;32:1689-92. 136. Jacobson P, Ng J, Ratanatharathorn V, Uberti J, Brundage RC. Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients. Bone Marrow Transplant 2001;28:753-8. 137. Staatz CE, Willis C, Taylor PJ, Lynch SV, Tett SE. Toward better outcomes with tacrolimus therapy: population pharmacokinetics and individualized dosage prediction in adult liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2003;9:130-7. 138. Katsakiori PF, Papapetrou EP, Sakellaropoulos GC, Goumenos DS, Nikiforidis GC, Flordellis CS. Factors affecting the long-term response to tacrolimus in renal transplant patients: pharmacokinetic and pharmacogenetic approach. Int J Med Sci 2010;7:94-100. 139. Hu RH, Lee PH, Chung YC, Huang MT, Lee CS. Hepatitis B and C in renal transplantation in Taiwan. Transplant Proc 1994;26:2059-61. 140. Kahan BD, Kramer WG, Wideman C, Flechner SM, Lorber MI, Van Buren CT. Demographic factors affecting the pharmacokinetics of cyclosporine estimated by radioimmunoassay. Transplantation 1986;41:459-64. 141. Manzanares C, Moreno M, Castellanos F, et al. Influence of hepatitis C virus infection on FK 506 blood levels in renal transplant patients. Transplant Proc 1998;30:1264-5. 142. Horina JH, Wirnsberger GH, Kenner L, Holzer H, Krejs GJ. Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C. Transplantation 1993;56:1091-4. 143. Baran DA, Galin I, Sandler D, et al. Tacrolimus in cardiac transplantation: efficacy and safety of a novel dosing protocol. Transplantation 2002;74:1136-41. 144. Warty V, Venkataramanan R, Zendehrouh P, et al. Distribution of FK 506 in plasma lipoproteins in transplant patients. Transplant Proc 1991;23:954-5. 145. Bauer LA. Applied clinical pharmacokinetics. 2 ed. New York: McGraw-Hill; 2008. 146. Zahir H, McLachlan AJ, Nelson A, McCaughan G, Gleeson M, Akhlaghi F. Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. Therapeutic drug monitoring 2005;27:422-30. 147. Golubovic B, Vucicevic K, Radivojevic D, Kovacevic SV, Prostran M, Miljkovic B. Total plasma protein effect on tacrolimus elimination in kidney transplant patients--population pharmacokinetic approach. Eur J Pharm Sci 2014;52:34-40. 148. Barraclough KA, Isbel NM, Johnson DW, Campbell SB, Staatz CE. Once- versus twice-daily tacrolimus: are the formulations truly equivalent? Drugs 2011;71:1561-77. 149. Hougardy JM, de Jonge H, Kuypers D, Abramowicz D. The once-daily formulation of tacrolimus: a step forward in kidney transplantation? Transplantation 2012;93:241-3. 150. Alloway R, Steinberg S, Khalil K, et al. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc 2005;37:867-70. 151. Florman S, Alloway R, Kalayoglu M, et al. Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen. Transplant Proc 2005;37:1211-3. 152. Cross SA, Perry CM. Tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients. Drugs 2007;67:1931-43. 153. Wlodarczyk Z, Squifflet JP, Ostrowski M, et al. Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2009;9:2505-13. 154. de Jonge H, Kuypers DR, Verbeke K, Vanrenterghem Y. Reduced C0 concentrations and increased dose requirements in renal allograft recipients converted to the novel once-daily tacrolimus formulation. Transplantation 2010;90:523-9. 155. Wu MJ, Cheng CY, Chen CH, et al. Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients. Transplantation 2011;92:648-52. 156. Hougardy JM, Broeders N, Kianda M, et al. Conversion from Prograf to Advagraf among kidney transplant recipients results in sustained decrease in tacrolimus exposure. Transplantation 2011;91:566-9. 157. Crespo M, Mir M, Marin M, et al. De novo kidney transplant recipients need higher doses of Advagraf compared with Prograf to get therapeutic levels. Transplant Proc 2009;41:2115-7. 158. Horowitz M, Fraser RJ. Gastroparesis: diagnosis and management. Scandinavian journal of gastroenterology Supplement 1995;213:7-16. 159. van Duijnhoven E, Christiaans M, Schafer A, Undre N, van Hooff J. Tacrolimus dosing requirements in diabetic and nondiabetic patients calculated from pretransplantation data. Transplant Proc 1998;30:1266-7. 160. Morgan ET. Regulation of cytochromes P450 during inflammation and infection. Drug Metab Rev 1997;29:1129-88. 161. Iber H, Sewer MB, Barclay TB, Mitchell SR, Li T, Morgan ET. Modulation of drug metabolism in infectious and inflammatory diseases. Drug Metab Rev 1999;31:29-41. 162. Christians U, Jacobsen W, Benet LZ, Lampen A. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clinical pharmacokinetics 2002;41:813-51. 163. Hronova K, Sima M, Svetlik S, Matouskova O, Slanar O. Pharmacogenetics and immunosuppressive drugs. Expert Rev Clin Pharmacol 2014;7:821-35. 164. Li JL, Wang XD, Chen SY, et al. Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective. The pharmacogenomics journal 2011;11:300-6. 165. Kuehl P, Zhang J, Lin Y, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nature genetics 2001;27:383-91. 166. McCarthy AD, Kennedy JL, Middleton LT. Pharmacogenetics in drug development. Philosophical transactions of the Royal Society of London Series B, Biological sciences 2005;360:1579-88. 167. Walker DK. The use of pharmacokinetic and pharmacodynamic data in the assessment of drug safety in early drug development. British journal of clinical pharmacology 2004;58:601-8. 168. Hesselink DA, van Schaik RH, van der Heiden IP, et al. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003;74:245-54. 169. Wehland M, Bauer S, Brakemeier S, et al. Differential impact of the CYP3A5*1 and CYP3A5*3 alleles on pre-dose concentrations of two tacrolimus formulations. Pharmacogenetics and genomics 2011;21:179-84. 170. Thervet E, Anglicheau D, King B, et al. Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients. Transplantation 2003;76:1233-5. 171. Haufroid V, Mourad M, Van Kerckhove V, et al. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 2004;14:147-54. 172. Macphee IA, Fredericks S, Mohamed M, et al. Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians. Transplantation 2005;79:499-502. 173. Zhao Y, Song M, Guan D, et al. Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus. Transplant Proc 2005;37:178-81. 174. Haufroid V, Wallemacq P, VanKerckhove V, et al. CYP3A5 and ABCB1 polymorphisms and tacrolimus pharmacokinetics in renal transplant candidates: guidelines from an experimental study. Am J Transplant 2006;6:2706-13. 175. Roy JN, Barama A, Poirier C, Vinet B, Roger M. Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients. Pharmacogenet Genomics 2006;16:659-65. 176. Rong G, Jing L, Deng-Qing L, Hong-Shan Z, Shai-Hong Z, Xin-Min N. Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients. Transplant Proc 2010;42:3455-8. 177. Ferraresso M, Turolo S, Ghio L, et al. Association between CYP3A5 polymorphisms and blood pressure in kidney transplant recipients receiving calcineurin inhibitors. Clinical and experimental hypertension (New York, NY : 1993) 2011;33:359-65. 178. Tang HL, Xie HG, Yao Y, Hu YF. Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers. Pharmacogenet Genomics 2011;21:713-20. 179. Terrazzino S, Quaglia M, Stratta P, Canonico PL, Genazzani AA. The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients: a systematic review and meta-analysis. Pharmacogenet Genomics 2012;22:642-5. 180. Thervet E, Loriot MA, Barbier S, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther 2010;87:721-6. 181. Shuker N, Bouamar R, van Schaik RH, et al. A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation. Am J Transplant 2016;16:2085-96. 182. Passey C, Birnbaum AK, Brundage RC, Oetting WS, Israni AK, Jacobson PA. Dosing equation for tacrolimus using genetic variants and clinical factors. Br J Clin Pharmacol 2011;72:948-57. 183. Zuo XC, Ng CM, Barrett JS, et al. Effects of CYP3A4 and CYP3A5 polymorphisms on tacrolimus pharmacokinetics in Chinese adult renal transplant recipients: a population pharmacokinetic analysis. Pharmacogenet Genomics 2013;23:251-61. 184. Uesugi M, Hosokawa M, Shinke H, et al. Influence of cytochrome P450 (CYP) 3A4*1G polymorphism on the pharmacokinetics of tacrolimus, probability of acute cellular rejection, and mRNA expression level of CYP3A5 rather than CYP3A4 in living-donor liver transplant patients. Biological & pharmaceutical bulletin 2013;36:1814-21. 185. Fukushima-Uesaka H, Saito Y, Watanabe H, et al. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Human mutation 2004;23:100. 186. Shi XJ, Geng F, Jiao Z, Cui XY, Qiu XY, Zhong MK. Association of ABCB1, CYP3A4*18B and CYP3A5*3 genotypes with the pharmacokinetics of tacrolimus in healthy Chinese subjects: a population pharmacokinetic analysis. J Clin Pharm Ther 2011;36:614-24. 187. Li DY, Teng RC, Zhu HJ, Fang Y. CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients. International journal of clinical pharmacology and therapeutics 2013;51:466-74. 188. Elens L, Sombogaard F, Hesselink DA, van Schaik RH, van Gelder T. Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome proliferator-activated receptor-alpha are associated with the development of new-onset diabetes after transplantation in kidney transplant recipients treated with tacrolimus. Pharmacogenetics and genomics 2013;23:649-57. 189. Elens L, Nieuweboer AJ, Clarke SJ, et al. Impact of POR*28 on the clinical pharmacokinetics of CYP3A phenotyping probes midazolam and erythromycin. Pharmacogenetics and genomics 2013;23:148-55. 190. Lesche D, Sigurdardottir V, Setoud R, et al. CYP3A5*3 and POR*28 genetic variants influence the required dose of tacrolimus in heart transplant recipients. Therapeutic drug monitoring 2014;36:710-5. 191. de Jonge H, Metalidis C, Naesens M, Lambrechts D, Kuypers DR. The P450 oxidoreductase *28 SNP is associated with low initial tacrolimus exposure and increased dose requirements in CYP3A5-expressing renal recipients. Pharmacogenomics 2011;12:1281-91. 192. Elens L, Hesselink DA, Bouamar R, et al. Impact of POR*28 on the pharmacokinetics of tacrolimus and cyclosporine A in renal transplant patients. Ther Drug Monit 2014;36:71-9. 193. Gijsen VM, van Schaik RH, Soldin OP, et al. P450 oxidoreductase *28 (POR*28) and tacrolimus disposition in pediatric kidney transplant recipients--a pilot study. Therapeutic drug monitoring 2014;36:152-8. 194. Jannot AS, Vuillemin X, Etienne I, et al. A Lack of Significant Effect of POR*28 Allelic Variant on Tacrolimus Exposure in Kidney Transplant Recipients. Ther Drug Monit 2016;38:223-9. 195. Juranka PF, Zastawny RL, Ling V. P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1989;3:2583-92. 196. Canaparo R, Finnstrom N, Serpe L, et al. Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum. Clinical and experimental pharmacology & physiology 2007;34:1138-44. 197. Cascorbi I. P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations. Handbook of experimental pharmacology 2011:261-83. 198. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proceedings of the National Academy of Sciences of the United States of America 2000;97:3473-8. 199. Anglicheau D, Flamant M, Schlageter MH, et al. Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2003;18:2409-14. 200. Wang W, Zhang XD, Ma LL, et al. [Relationship between MDR1 gene polymorphism and blood concentration of tacrolimus in renal transplant patients]. Zhonghua yi xue za zhi 2005;85:3277-81. 201. Hesselink DA, van Schaik RH, van Agteren M, et al. CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients. Pharmacogenet Genomics 2008;18:339-48. 202. Li Y, Hu X, Cai B, et al. Meta-analysis of the effect of MDR1 C3435 polymorphism on tacrolimus pharmacokinetics in renal transplant recipients. Transplant immunology 2012;27:12-8. 203. Jordan de Luna C, Herrero Cervera MJ, Sanchez Lazaro I, Almenar Bonet L, Poveda Andres JL, Alino Pellicer SF. Pharmacogenetic study of ABCB1 and CYP3A5 genes during the first year following heart transplantation regarding tacrolimus or cyclosporine levels. Transplant Proc 2011;43:2241-3. 204. Provenzani A, Notarbartolo M, Labbozzetta M, et al. Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients. Int J Mol Med 2011;28:1093-102. 205. Hawwa AF, McKiernan PJ, Shields M, Millership JS, Collier PS, McElnay JC. Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant. British journal of clinical pharmacology 2009;68:413-21. 206. Hawwa AF, McElnay JC. Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant. Expert opinion on drug safety 2011;10:9-22. 207. Fukudo M, Yano I, Masuda S, et al. Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients. Clinical pharmacology and therapeutics 2006;80:331-45. 208. Zhang J, Zhang X, Liu L, Tong W. Value of CYP3A5 genotyping on determining initial dosages of tacrolimus for Chinese renal transplant recipients. Transplant Proc 2010;42:3459-64. 209. Chen JS, Li LS, Cheng DR, et al. Effect of CYP3A5 genotype on renal allograft recipients treated with tacrolimus. Transplant Proc 2009;41:1557-61. 210. Li L, Li CJ, Zheng L, et al. Tacrolimus dosing in Chinese renal transplant recipients: a population-based pharmacogenetics study. Eur J Clin Pharmacol 2011;67:787-95. 211. Chen SY, Li JL, Meng FH, et al. Individualization of tacrolimus dosage basing on cytochrome P450 3A5 polymorphism--a prospective, randomized, controlled study. Clin Transplant 2013;27:E272-81. 212. Chen P, Li J, Li J, et al. Dynamic effects of CYP3A5 polymorphism on dose requirement and trough concentration of tacrolimus in renal transplant recipients. J Clin Pharm Ther 2016. 213. Hirano K, Naito T, Mino Y, Takayama T, Ozono S, Kawakami J. Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients. Clinica chimica acta; international journal of clinical chemistry 2012;414:120-4. 214. Satoh S, Saito M, Inoue T, et al. CYP3A5 *1 allele associated with tacrolimus trough concentrations but not subclinical acute rejection or chronic allograft nephropathy in Japanese renal transplant recipients. Eur J Clin Pharmacol 2009;65:473-81. 215. Kato H, Usui M, Muraki Y, et al. Long-Term Influence of CYP3A5 Gene Polymorphism on Pharmacokinetics of Tacrolimus and Patient Outcome After Living Donor Liver Transplantation. Transplant Proc 2016;48:1087-94. 216. Miyata Y, Akamatsu N, Sugawara Y, et al. Pharmacokinetics of a Once-Daily Dose of Tacrolimus Early After Liver Transplantation: With Special Reference to CYP3A5 and ABCB1 Single Nucleotide Polymorphisms. Annals of transplantation 2016;21:491-9. 217. Niioka T, Kagaya H, Miura M, et al. Pharmaceutical and genetic determinants for interindividual differences of tacrolimus bioavailability in renal transplant recipients. Eur J Clin Pharmacol 2013;69:1659-65. 218. Cho JH, Yoon YD, Park JY, et al. Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. Transplant Proc 2012;44:109-14. 219. Jun KR, Lee W, Jang MS, et al. Tacrolimus concentrations in relation to CYP3A and ABCB1 polymorphisms among solid organ transplant recipients in Korea. Transplantation 2009;87:1225-31. 220. Min SI, Kim SY, Ahn SH, et al. CYP3A5 *1 allele: impacts on early acute rejection and graft function in tacrolimus-based renal transplant recipients. Transplantation 2010;90:1394-400. 221. Ro H, Min SI, Yang J, et al. Impact of tacrolimus intraindividual variability and CYP3A5 genetic polymorphism on acute rejection in kidney transplantation. Ther Drug Monit 2012;34:680-5. 222. de Wildt SN, van Schaik RH, Soldin OP, et al. The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation. Eur J Clin Pharmacol 2011;67:1231-41. 223. Alvarez-Elias AC, Garcia-Roca P, Velasquez-Jones L, Valverde S, Varela-Fascinetto G, Medeiros M. CYP3A5 Genotype and Time to Reach Tacrolimus Therapeutic Levels in Renal Transplant Children. Transplant Proc 2016;48:631-4. 224. Buendia JA, Otamendi E, Kravetz MC, et al. Combinational Effect of CYP3A5 and MDR-1 Polymorphisms on Tacrolimus Pharmacokinetics in Liver Transplant Patients. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 2015;13:441-8. 225. Miura M, Satoh S, Kagaya H, et al. Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients. Pharmacogenomics 2011;12:977-84. 226. Zhu L, Zhang J, Song H, et al. Relationships of related genetic polymorphisms and individualized medication of tacrolimus in patients with renal transplantation. International journal of clinical and experimental medicine 2015;8:19006-13. 227. Zhang JJ, Zhang H, Ding XL, Ma S, Miao LY. Effect of the P450 oxidoreductase 28 polymorphism on the pharmacokinetics of tacrolimus in Chinese healthy male volunteers. Eur J Clin Pharmacol 2013;69:807-12. 228. Miao LY, Huang CR, Hou JQ, Qian MY. Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients. Biopharmaceutics & drug disposition 2008;29:1-5. 229. Yan L, Li Y, Tang JT, An YF, Wang LL, Shi YY. Donor ABCB1 3435 C>T genetic polymorphisms influence early renal function in kidney transplant recipients treated with tacrolimus. Pharmacogenomics 2016;17:249-57. 230. Turolo S, Tirelli AS, Ferraresso M, et al. Frequencies and roles of CYP3A5, CYP3A4 and ABCB1 single nucleotide polymorphisms in Italian teenagers after kidney transplantation. Pharmacological reports : PR 2010;62:1159-69. 231. Prytula AA, Cransberg K, Bouts AH, et al. The Effect of Weight and CYP3A5 Genotype on the Population Pharmacokinetics of Tacrolimus in Stable Paediatric Renal Transplant Recipients. Clin Pharmacokinet 2016;55:1129-43. 232. Stefanovic NZ, Cvetkovic TP, Jevtovic-Stoimenov TM, Ignjatovic AM, Paunovic GJ, Velickovic RM. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function. Experimental and therapeutic medicine 2015;10:1149-56. 233. Tacrolimus. Drugdex Informaction System. Micromedex; 2016. 234. ABBOTT ARCHITECT Tacrolimus package insert. 2009. 235. Rancic N, Dragojevic-Simic V, Vavic N, et al. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: the influence of gender and comedication. Vojnosanitetski pregled 2015;72:813-22. 236. Velickovic-Radovanovic R, Mikov M, Catic-Djordjevic A, et al. Gender-dependent predictable pharmacokinetic method for tacrolimus exposure monitoring in kidney transplant patients. European journal of drug metabolism and pharmacokinetics 2015;40:95-102. 237. Lemahieu WP, Maes BD, Verbeke K, Vanrenterghem YF. Alterations of CYP3A4 and P-glycoprotein activity in vivo with time in renal graft recipients. Kidney Int 2004;66:433-40. 238. Luo X, Zhu LJ, Cai NF, Zheng LY, Cheng ZN. Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients. Acta pharmacologica Sinica 2016;37:555-60. 239. Bruckmueller H, Werk AN, Renders L, et al. Which Genetic Determinants Should be Considered for Tacrolimus Dose Optimization in Kidney Transplantation? A Combined Analysis of Genes Affecting the CYP3A Locus. Therapeutic drug monitoring 2015;37:288-95. 240. Shi S, Morike K, Klotz U. The clinical implications of ageing for rational drug therapy. European journal of clinical pharmacology 2008;64:183-99. 241. Zeeh J, Platt D. The aging liver: structural and functional changes and their consequences for drug treatment in old age. Gerontology 2002;48:121-7. 242. Hesselink DA, Bouamar R, Elens L, van Schaik RH, van Gelder T. The role of pharmacogenetics in the disposition of and response to tacrolimus in solid organ transplantation. Clin Pharmacokinet 2014;53:123-39. 243. Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clinical pharmacokinetics 2005;44:33-60. 244. Staatz CE, Tett SE. Pharmacokinetic considerations relating to tacrolimus dosing in the elderly. Drugs & aging 2005;22:541-57. 245. Storset E, Holford N, Midtvedt K, Bremer S, Bergan S, Asberg A. Importance of hematocrit for a tacrolimus target concentration strategy. European journal of clinical pharmacology 2014;70:65-77. 246. Shi YY, Hesselink DA, van Gelder T. Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients. Transplantation reviews 2015;29:224-30. 247. Storset E, Holford N, Hennig S, et al. Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling. British journal of clinical pharmacology 2014;78:509-23. 248. Pichard L, Fabre I, Fabre G, et al. Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos 1990;18:595-606. 249. Hesselink DA, Ngyuen H, Wabbijn M, et al. Tacrolimus dose requirement in renal transplant recipients is significantly higher when used in combination with corticosteroids. Br J Clin Pharmacol 2003;56:327-30. 250. Park SI, Felipe CR, Pinheiro-Machado PG, et al. Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus. Fundamental & clinical pharmacology 2009;23:137-45. 251. Picard N, Cresteil T, Premaud A, Marquet P. Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Therapeutic drug monitoring 2004;26:600-8. 252. Fardel O, Jigorel E, Le Vee M, Payen L. Physiological, pharmacological and clinical features of the multidrug resistance protein 2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2005;59:104-14. 253. Pirsch J, Bekersky I, Vincenti F, et al. Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability. J Clin Pharmacol 2000;40:527-32. 254. Christians U, Strom T, Zhang YL, et al. Active drug transport of immunosuppressants: new insights for pharmacokinetics and pharmacodynamics. Therapeutic drug monitoring 2006;28:39-44. 255. Squifflet JP, Vanrenterghem Y, van Hooff JP, Salmela K, Rigotti P, European Tacrolimus MMFTSG. Safe withdrawal of corticosteroids or mycophenolate mofetil: results of a large, prospective, multicenter, randomized study. Transplant Proc 2002;34:1584-6. 256. Kagaya H, Miura M, Satoh S, et al. No pharmacokinetic interactions between mycophenolic acid and tacrolimus in renal transplant recipients. J Clin Pharm Ther 2008;33:193-201. 257. Pou L, Brunet M, Cantarell C, et al. Mycophenolic acid plasma concentrations: influence of comedication. Therapeutic drug monitoring 2001;23:35-8. 258. Ganschow R, Albani J, Grabhorn E, Richter A, Burdelski M. Tacrolimus-induced cholestatic syndrome following pediatric liver transplantation and steroid-resistant graft rejection. Pediatr Transplant 2006;10:220-4. 259. Wang J. CYP3A polymorphisms and immunosuppressive drugs in solid-organ transplantation. Expert review of molecular diagnostics 2009;9:383-90. 260. Numakura K, Satoh S, Tsuchiya N, et al. Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus. Transplantation 2005;80:1419-24. 261. Picard N, Bergan S, Marquet P, et al. Pharmacogenetic Biomarkers Predictive of the Pharmacokinetics and Pharmacodynamics of Immunosuppressive Drugs. Therapeutic drug monitoring 2016;38 Suppl 1:S57-69. 262. Li JL, Liu S, Fu Q, et al. Interactive effects of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tracrolimus trough concentrations in early postrenal transplant recipients. Pharmacogenomics 2015;16:1355-65. 263. Kimchi-Sarfaty C, Oh JM, Kim IW, et al. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science (New York, NY) 2007;315:525-8. 264. Wei-lin W, Jing J, Shu-sen Z, et al. Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients. Liver Transpl 2006;12:775-80. 265. Zheng H, Webber S, Zeevi A, et al. Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2003;3:477-83. 266. Kravljaca M, Perovic V, Pravica V, et al. The importance of MDR1 gene polymorphisms for tacrolimus dosage. Eur J Pharm Sci 2016;83:109-13. 267. Cheung CY, Op den Buijsch RA, Wong KM, et al. Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients. Pharmacogenomics 2006;7:563-74. 268. Christians U, Schmidt G, Bader A, et al. Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. Br J Clin Pharmacol 1996;41:187-90. 269. Ibrahim RB, Abella EM, Chandrasekar PH. Tacrolimus-clarithromycin interaction in a patient receiving bone marrow transplantation. Ann Pharmacother 2002;36:1971-2. 270. Wolter K, Wagner K, Philipp T, Fritschka E. Interaction between FK 506 and clarithromycin in a renal transplant patient. Eur J Clin Pharmacol 1994;47:207-8. 271. Furlan V, Perello L, Jacquemin E, Debray D, Taburet AM. Interactions between FK506 and rifampicin or erythromycin in pediatric liver recipients. Transplantation 1995;59:1217-8. 272. Shaeffer MS, Collier D, Sorrell MF. Interaction between FK506 and erythromycin. Ann Pharmacother 1994;28:280-1. 273. Iwasaki K, Matsuda H, Nagase K, Shiraga T, Tokuma Y, Uchida K. Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes. Res Commun Chem Pathol Pharmacol 1993;82:209-16. 274. Matsuda H, Iwasaki K, Shiraga T, Tozuka Z, Hata T, Guengerich FP. Interactions of FK506 (tacrolimus) with clinically important drugs. Res Commun Mol Pathol Pharmacol 1996;91:57-64. 275. Prasad TN, Stiff DD, Subbotina N, et al. FK 506 (Tacrolimus) metabolism by rat liver microsomes and its inhibition by other drugs. Res Commun Chem Pathol Pharmacol 1994;84:35-46. 276. Mieles L, Venkataramanan R, Yokoyama I, Warty VJ, Starzl TE. Interaction between FK506 and clotrimazole in a liver transplant recipient. Transplantation 1991;52:1086-7. 277. Herzig K, Johnson DW. Marked elevation of blood cyclosporin and tacrolimus levels due to concurrent metronidazole therapy. Nephrol Dial Transplant 1999;14:521-3. 278. Page RL, 2nd, Klem PM, Rogers C. Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy. Ann Pharmacother 2005;39:1109-13. 279. Roedler R, Neuhauser MM, Penzak SR. Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? Ann Pharmacother 2007;41:653-8. 280. Assan R, Fredj G, Larger E, Feutren G, Bismuth H. FK 506/fluconazole interaction enhances FK 506 nephrotoxicity. Diabete Metab 1994;20:49-52. 281. Osowski CL, Dix SP, Lin LS, Mullins RE, Geller RB, Wingard JR. Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. Transplantation 1996;61:1268-72. 282. Toda F, Tanabe K, Ito S, et al. Tacrolimus trough level adjustment after administration of fluconazole to kidney recipients. Transplant Proc 2002;34:1733-5. 283. Capone D, Gentile A, Imperatore P, Palmiero G, Basile V. Effects of itraconazole on tacrolimus blood concentrations in a renal transplant recipient. Ann Pharmacother 1999;33:1124-5. 284. Furlan V, Parquin F, Penaud JF, et al. Interaction between tacrolimus and itraconazole in a heart-lung transplant recipient. Transplant Proc 1998;30:187-8. 285. Tuteja S, Alloway RR, Johnson JA, Gaber AO. The effect of gut metabolism on tacrolimus bioavailability in renal transplant recipients. Transplantation 2001;71:1303-7. 286. Pai MP, Allen S. Voriconazole inhibition of tacrolimus metabolism. Clin Infect Dis 2003;36:1089-91. 287. Venkataramanan R, Zang S, Gayowski T, Singh N. Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes. Antimicrob Agents Chemother 2002;46:3091-3. 288. Berge M, Chevalier P, Benammar M, et al. Safe management of tacrolimus together with posaconazole in lung transplant patients with cystic fibrosis. Ther Drug Monit 2009;31:396-9. 289. De Lima JJ, Xue H, Coburn L, et al. Effects of FK506 in rat and human resistance arteries. Kidney Int 1999;55:1518-27. 290. Homma M, Itagaki F, Yuzawa K, Fukao K, Kohda Y. Effects of lansoprazole and rabeprazole on tacrolimus blood concentration: case of a renal transplant recipient with CYP2C19 gene mutation. Transplantation 2002;73:303-4. 291. Itagaki F, Homma M, Yuzawa K, Fukao K, Kohda Y. Drug interaction of tacrolimus and proton pump inhibitors in renal transplant recipients with CYP2C19 gene mutation. Transplant Proc 2002;34:2777-8. 292. Furuta S, Kamada E, Suzuki T, et al. Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica 2001;31:1-10. 293. Regazzi MB, Iacona I, Alessiani M, et al. Interaction between FK 506 and diltiazem in an animal model. Transplant Proc 1996;28:1017-8. 294. Tada H, Yanagiwara S, Ito K, Suzuki T. Role of diltiazem on tacrolimus pharmacokinetics in tacrolimus-induced nephrotoxic rats. Pharmacol Toxicol 1999;84:241-6. 295. Hebert MF, Lam AY. Diltiazem increases tacrolimus concentrations. Ann Pharmacother 1999;33:680-2. 296. Hooper DK, Fukuda T, Gardiner R, et al. Risk of tacrolimus toxicity in CYP3A5 nonexpressors treated with intravenous nicardipine after kidney transplantation. Transplantation 2012;93:806-12. 297. Hurst AL, Clark N, Carpenter TC, Sundaram SS, Reiter PD. Supra-therapeutic tacrolimus concentrations associated with concomitant nicardipine in pediatric liver transplant recipients. Pediatr Transplant 2015;19:E83-7. 298. Olyaei AJ, deMattos AM, Norman DJ, Bennett WM. Interaction between tacrolimus and nefazodone in a stable renal transplant recipient. Pharmacotherapy 1998;18:1356-9. 299. Boubenider S, Vincent I, Lambotte O, et al. Interaction between theophylline and tacrolimus in a renal transplant patient. Nephrol Dial Transplant 2000;15:1066-8. 300. Sheikh AM, Wolf DC, Lebovics E, Goldberg R, Horowitz HW. Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels. Transplantation 1999;68:307-9. 301. Schvarcz R, Rudbeck G, Soderdahl G, Stahle L. Interaction between nelfinavir and tacrolimus after orthoptic liver transplantation in a patient coinfected with HIV and hepatitis C virus (HCV). Transplantation 2000;69:2194-5. 302. Jain AK, Venkataramanan R, Shapiro R, et al. Interaction between tacrolimus and antiretroviral agents in human immunodeficiency virus-positive liver and kidney transplantation patients. Transplant Proc 2002;34:1540-1. 303. van de Plas A, Dackus J, Christiaans MH, Stolk LM, van Hooff JP, Neef C. A pilot study on sublingual administration of tacrolimus. Transpl Int 2009;22:358-9. 304. Seifeldin RA, Marcos-Alvarez A, Gordon FD, Lewis WD, Jenkins RL. Nifedipine interaction with tacrolimus in liver transplant recipients. Ann Pharmacother 1997;31:571-5. 305. Zuo XC, Zhou YN, Zhang BK, et al. Effect of CYP3A5*3 polymorphism on pharmacokinetic drug interaction between tacrolimus and amlodipine. Drug metabolism and pharmacokinetics 2013;28:398-405. 306. Zhao W, Baudouin V, Fakhoury M, Storme T, Deschenes G, Jacqz-Aigrain E. Pharmacokinetic interaction between tacrolimus and amlodipine in a renal transplant child. Transplantation 2012;93:e29-30. 307. Mathis AS, Shah N, Knipp GT, Friedman GS. Interaction of chloramphenicol and the calcineurin inhibitors in renal transplant recipients. Transpl Infect Dis 2002;4:169-74. 308. Schulman SL, Shaw LM, Jabs K, Leonard MB, Brayman KL. Interaction between tacrolimus and chloramphenicol in a renal transplant recipient. Transplantation 1998;65:1397-8. 309. Mignat C. Clinically significant drug interactions with new immunosuppressive agents. Drug Saf 1997;16:267-78. 310. Zhou SF, Xue CC, Yu XQ, Li C, Wang G. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007;29:687-710. 311. Finch CK, Chrisman CR, Baciewicz AM, Self TH. Rifampin and rifabutin drug interactions: an update. Arch Intern Med 2002;162:985-92. 312. Hebert MF, Fisher RM, Marsh CL, Dressler D, Bekersky I. Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999;39:91-6. 313. Kiuchi T, Tanaka K, Inomata Y, et al. Experience of tacrolimus-based immunosuppression in living-related liver transplantation complicated with graft tuberculosis: interaction with rifampicin and side effects. Transplant Proc 1996;28:3171-2. 314. Chenhsu RY, Loong CC, Chou MH, Lin MF, Yang WC. Renal allograft dysfunction associated with rifampin-tacrolimus interaction. Ann Pharmacother 2000;34:27-31. 315. Bhaloo S, Prasad GV. Severe reduction in tacrolimus levels with rifampin despite multiple cytochrome P450 inhibitors: a case report. Transplant Proc 2003;35:2449-51. 316. Sherry ST WM, Kholodov M et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001;29(1):308-11. 317. Akbas SH, Bilgen T, Keser I, et al. The effect of MDR1 (ABCB1) polymorphism on the pharmacokinetic of tacrolimus in Turkish renal transplant recipients. Transplant Proc 2006;38:1290-2. 318. Op den Buijsch RA, Christiaans MH, Stolk LM, et al. Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundamental & clinical pharmacology 2007;21:427-35. 319. Loh PT, Lou HX, Zhao Y, Chin YM, Vathsala A. Significant impact of gene polymorphisms on tacrolimus but not cyclosporine dosing in Asian renal transplant recipients. Transplant Proc 2008;40:1690-5. 320. Tirelli S, Ferraresso M, Ghio L, et al. The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients. Medical science monitor : international medical journal of experimental and clinical research 2008;14:Cr251-4. 321. Singh R, Srivastava A, Kapoor R, R KS, R DM. Impact of CYP3A5 and CYP3A4 gene polymorphisms on dose requirement of calcineurin inhibitors, cyclosporine and tacrolimus, in renal allograft recipients of North India. Naunyn-Schmiedeberg's archives of pharmacology 2009;380:169-77. 322. Kuypers DR, de Jonge H, Naesens M, Vanrenterghem Y. A prospective, open-label, observational clinical cohort study of the association between delayed renal allograft function, tacrolimus exposure, and CYP3A5 genotype in adult recipients. Clinical therapeutics 2010;32:2012-23. 323. Elens L, Bouamar R, Hesselink DA, et al. A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients. Clin Chem 2011;57:1574-83. 324. Elens L, van Schaik RH, Panin N, et al. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics 2011;12:1383-96. 325. Ferraris JR, Argibay PF, Costa L, et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids. Pediatr Transplant 2011;15:525-32. 326. Singh R, Srivastava A, Kapoor R, Mittal RD. Do drug transporter (ABCB1) SNPs influence cyclosporine and tacrolimus dose requirements and renal allograft outcome in the posttransplantation period? J Clin Pharmacol 2011;51:603-15. 327. Tavira B, Coto E, Diaz-Corte C, et al. Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes. Clinical chemistry and laboratory medicine 2011;49:825-33. 328. Elens L, Hesselink DA, van Schaik RH, van Gelder T. The CYP3A4*22 allele affects the predictive value of a pharmacogenetic algorithm predicting tacrolimus predose concentrations. Br J Clin Pharmacol 2013;75:1545-7. 329. Tavira B, Coto E, Diaz-Corte C, Alvarez V, Lopez-Larrea C, Ortega F. A search for new CYP3A4 variants as determinants of tacrolimus dose requirements in renal-transplanted patients. Pharmacogenet Genomics 2013;23:445-8. 330. Kurzawski M, Dabrowska J, Dziewanowski K, Domanski L, Peruzynska M, Drozdzik M. CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients. Pharmacogenomics 2014;15:179-88. 331. Genvigir FD, Salgado PC, Felipe CR, et al. Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients. Pharmacogenet Genomics 2016;26:462-72. 332. Yaowakulpatana K, Vadcharavivad S, Ingsathit A, et al. Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation. Eur J Clin Pharmacol 2016;72:277-83. 333. Yousef AM, Qosa H, Bulatova N, et al. Effects of Genetic Polymorphism in CYP3A4 and CYP3A5 Genes on Tacrolimus Dose Among Kidney Transplant Recipients. Iranian journal of kidney diseases 2016;10:156-63. 334. Lloberas N, Elens L, Llaudo I, et al. The combination of CYP3A4*22 and CYP3A5*3 single-nucleotide polymorphisms determines tacrolimus dose requirement after kidney transplantation. Pharmacogenet Genomics 2017;27:313-22. 335. Soda M, Fujitani M, Michiuchi R, et al. Association Between Tacrolimus Pharmacokinetics and Cytochrome P450 3A5 and Multidrug Resistance Protein 1 Exon 21 Polymorphisms. Transplant Proc 2017;49:1492-8. 336. Zhang HJ, Li DY, Zhu HJ, Fang Y, Liu TS. Tacrolimus population pharmacokinetics according to CYP3A5 genotype and clinical factors in Chinese adult kidney transplant recipients. J Clin Pharm Ther 2017;42:425-32. 337. Asempa TE, Rebellato LM, Hudson S, Briley K, Maldonado AQ. Impact of CYP3A5 genomic variances on clinical outcomes among African American kidney transplant recipients. Clin Transplant 2018;32. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7510 | - |
dc.description.abstract | 臨床觀察發現腎臟移植的病人,即便使用相同劑量的tacrolimus(TAC),個體間的血中濃度變異還是很大。過去研究發現有許多臨床因素以及基因多型性可能會影響TAC的血中濃度,然而所獲得的結果缺乏一致性。本研究是第一個將所有可能影響TAC血中濃度的因素納入分析,探討各種因素對臺灣腎臟移植病人TAC血中濃度影響的研究。本研究於2008年1月1日至2015年7月31日所有在本醫學中心接受腎臟移植的病人中,選取移植後使用TAC作為免疫抑制劑且持續服用至少6個月,移植時的年齡介於20到65歲的病人。排除條件包含再移植或多重器官移植、非臺灣人以及人類免疫缺乏病毒反應呈陽性的病人。將研究期間仍持續追蹤並同意參與此臨床試驗,簽署受試者知情同意書(informed consent)後,取得檢體進行基因多型性分析的病人納入本研究。本研究中TAC主要以劑量調整谷濃度(dose normalized trough concentrations,dnC0;與dosing weight and dose normalized trough concentrations,dnC0/DW)作為藥動學參數,並在迴歸分析時進行對數轉換,確保資料符合常態分布。使用三個評估點:腎臟移植出院前、移植後3個月以及移植後6個月。統計方法在挑選候選因子以及綜合臨床及基因多型性因素分析時分別使用單變項及多元迴歸分析,連續性資料使用獨立樣本t檢定或曼恩-惠尼U檢定,同一病人在不同時間點的TAC濃度資料與檢驗數值使用單因子重複量測變異數分析、類別資料如性別及基因多型性等則使用Chi-squared test以及Fisher’s exact test。本研究納入98個腎臟移植病人,經多元迴歸分析,發現CYP3A5*3基因型在3個時間點皆為影響TAC ln dnC0或ln dnC0/DW最重要的因子,R2值介於0.35至0.45,且隨著時間增加。其他有顯著影響力的基因型包括ABCB1 (C3435T)以及ABCB1 (G2677T/A),但解釋力不高。ABCB1 (C3435T)基因型在移植手術出院前和移植後6個月的R2值分別為0.05和0.02;ABCB1 (G2677T/A) 基因型移植後3個月的R2值為0.05。顯著影響TAC ln dnC0或ln dnC0/DW的臨床因素則在3個時間點間各有差異,解釋能力較低,總和的R2值介於0.10至0.15。在移植手術出院前重要的臨床因素有mycophenolate mofetil(MMF)或mycophenolate sodium(MPS)的每日劑量、移植時的年齡以及direct bilirubin(D-bil)。在移植後3個月為total bilirubin(T-bil)、類固醇的每日劑量、性別以及移植時的年齡;在移植後6個月為有無使用MMF或MPS、類固醇的每日劑量、D-bil以及hematocrit(Hct)。在次族群分析中,發現CYP3A5不表現者會更容易受到其他基因多型性的影響,包括ABCB1 (C3435T)以及ABCB1 (G2677T/A),其R2值在3個評估點單變項分析相較於全體病人分析時的0.02-0.07增加至0.15-0.20。此外,在CYP3A5表現者中,有高達82.2 %的病人同時帶有CYP3A4*1G變異,此變異同樣會使TAC的代謝增加;反之,在CYP3A5不表現者中,有92.2 %的病人未帶有CYP3A4*1G變異。顯示兩基因多型性在分配上有顯著相關。最後,比較移植後抗排斥藥物組合,發現有使用MMF或MPS的病人相對於未使用MMF或MPS的病人(二重療法),在移植後6個月內的3個評估點,其TAC dnC0有較高的趨勢,但未達到統計顯著。本研究也提供了完整的臺灣族群TAC相關代謝途徑的基因多型性分布頻率資料。其中,CYP3A5表現者與不表現者的比例分別為47 %及53 %。在腎臟移植的病人,CYP3A5*3基因型在移植後的六個月內都是影響TAC ln dnC0或ln dnC0/DW的最重要因素。因此,建議在發生TAC劑量調整困難的病人,可以考慮檢測病人的CYP3A5*3基因,作為未來TAC劑量調整的參考。影響TAC ln dnC0或ln dnC0/DW的臨床因素會隨著手術後時間而有些變化,當上述因子有顯著改變時,需要密切監測病人的TAC血中濃度。在次族群分析中發現CYP3A5不表現者會更容易受到其他基因多型性的影響,包括ABCB1 (C3435T)以及ABCB1 (G2677T/A),且CYP3A5*3與CYP3A4*1G兩個基因多型性在分配上有顯著相關。因此臨床上在參考及應用病人基因多型性資料時也應注意多個基因多型性之間的關連性。MMF及MPS兩個藥品對TAC藥動學的影響可能需要未來更多研究來解答。 | zh_TW |
dc.description.abstract | Large interindividual and intraindividual variations of tacrolimus (TAC) pharmacokinetics (PK) exist in renal transplant recipients. Many factors were reported to influence the PK of TAC. However, there are limited studies explored the influence of both clinical and genetic factors, esp. in Taiwanese renal transplant patients. This is the first study investigated both genetic and clinical factors that significantly influenced TAC PK in Taiwanese at three different time points after renal transplantation. This study recruited all the candidates from kidney transplant recipients who underwent transplantations in our medical center between January 1, 2008, and July 31, 2015, received TAC as immunosuppressant for at least 6 months, and transplanted at the age of 20 to 65 years. Exclusion criteria were retransplantation, multiorgan transplantation, non-Taiwanese subjects and human immunodeficiency virus (HIV) positive patients. All patients enrolled were followed up during study period and their blood samples were taken for genetic study after signing informed consent. The concentrations of TAC were dose normalized, including dnC0 (dose normalized trough concentrations) and dnC0/DW (dosing weight and dose normalized trough concentrations). These two variables were log-transformed in regression analyses to ensure a normal distribution. This study evaluated the dnC0 and dnC0/DW of TAC at three time points: the last steady state C0 before discharge for transplant surgery, 3 months after transplant and 6 months after transplant. Univariate and multiple regression were used to select the candidate independent variables and to identify the significant factors that influenced the ln dnC0 and ln dnC0/DW. Independent t-test or Mann-Whitney U test were used for continuous data. One-way Repeated Measurement ANOVA (analysis of variance) was used to compare lab data and TAC C0 within the same patient at different time points. Chi-squared test and Fisher's exact test were used for categorical data. A total of 98 kidney transplant recipients were enrolled in the study. At all time points, CYP3A5*3 polymorphism was the most significant factor associated with TAC ln dnC0 or ln dnC0/DW, with a R2 of 0.35-0.45, which increased over time. Other significant SNPs included ABCB1 (C3435T) and ABCB1 (G2677T/A), but the impact was small. The R2 of ABCB1 (C3435T) polymorphism at the time before discharge after transplantation and 6 months after transplant were 0.05 and 0.02, respectively. The R2 of ABCB1 (G2677T/A) polymorphism at three months after transplant was 0.05. Significant clinical factors varied at different time points, and only had a total R2 of 0.10-0.15. Before discharge after transplantation, age, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS) daily dose and direct bilirubin were significantly associated with TAC ln dnC0 or ln dnC0/DW. Significant clinical factor at 3 months after transplant included age, sex, daily dose of steroids and total bilirubin (T-bil); While at 6 months after transplant included MMF or MPS use, daily dose of steroids, direct bilirubin (D-bil) and hematocrit. In subgroup analyses, CYP3A5 nonexpressers were found to be more sensitive to other SNPs, including ABCB1 (C3435T) and ABCB1 (G2677T/A). Their R2 in univariate regression analysis at 3 time points increased from 0.02-0.07 to 0.15-0.20. We also found that 82.2 % of CYP3A5 expressers had at least one CYP3A4*1G mutation. In contrast, 92.2 % of CYP3A5 nonexpressers did not have CYP3A4*1G mutation. CYP3A4*1G polymorphism was strongly linked with the CYP3A5*3 polymorphism. Last but not least, the present study found that patients receiving MMF or MPS had higher TAC dnC0 compared to non-users (dual therapy) at all three time points, although the differences were not statistically significant. This study also provided comprehensive gene distribution data of SNPs related to TAC metabolism pathway in Taiwanese. The proportions CYP3A5 expressers and nonexpressers are 47 % and 53 % respectively. CYP3A5*3 polymorphism is the most important factor that influenced TAC ln dnC0 or ln dnC0/DW in renal transplant patients within 6 months after transplant. Thus, testing CYP3A5*3 polymorphism could serve as a reference for dosage adjustments in patients with difficulty in achieving TAC target concentration. The significant clinical factors varied at different time points and played a minimum role. TAC C0 should be closely monitored when there is a significant change in the factors mentioned above. This study showed that CYP3A5 nonexpressers were more sensitive to other SNPs, including ABCB1 (C3435T) and ABCB1 (G2677T/A). In addition, CYP3A4*1G polymorphism was strongly linked with the CYP3A5*3 polymorphism. The relationship between different SNPs should be considered when we apply patients’ genetic data on TAC dosage adjustments. Finally, future studies are needed to elucidate the influence of MMF/MPS on TAC PK. | en |
dc.description.provenance | Made available in DSpace on 2021-05-19T17:45:15Z (GMT). No. of bitstreams: 1 ntu-107-R05451008-1.pdf: 3529413 bytes, checksum: a3c2c7bfc4bd3897aec34d80223f5246 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 論文口試委員審定書 i
致謝 ii 縮寫表 iii 中文摘要 v Abstract viii 目錄 xi 圖目錄 xvi 表目錄 xvii 第一章、前言 1 第二章、文獻探討 3 2.1 腎臟移植的免疫抑制劑使用情形 3 2.2 Tacrolimus簡介 3 2.2.1 Tacrolimus的作用機制 4 2.2.2 Tacrolimus的毒性 5 2.3 Tacrolimus的藥動學特性 7 2.3.1 吸收 7 2.3.2 分布 7 2.3.3 代謝及排除 8 2.4 臨床因素對tacrolimus藥動學的影響 9 2.4.1 年齡 9 2.4.2 性別 10 2.4.3 移植後天數(post-operative day,POD) 10 2.4.4 肝功能 11 2.4.5 HBV(hepatitis B virus)與HCV(hepatitis C virus) 11 2.4.6 腎功能 12 2.4.7 白蛋白(Alb)與總蛋白(TP) 12 2.4.8 血紅素(hemoglobin,Hb)與血比容(Hct) 12 2.4.9 TAC製劑Prograf ®與Advagraf ® 13 2.4.10 糖尿病(diabetes mellitus,DM) 13 2.4.11 感染 13 2.5 藥品對tacrolimus藥動學的影響 14 2.6 基因多型性(gene polymorphism)對tacrolimus藥動學的影響 14 2.6.1 CYP3A5 15 2.6.2 CYP3A4 16 2.6.3 POR*28 17 2.6.4 ABCB1 17 2.7 與tacrolimus藥動學相關SNP之基因分布 18 2.7.1 CYP3A5 19 2.7.2 CYP3A4 20 2.7.3 POR*28 21 2.7.4 ABCB1 21 第三章、研究目的及方法 23 3.1 研究目的 23 3.2 研究方法 23 3.2.1 研究架構 23 3.2.2 病人 23 3.2.3 臨床資訊收集之流程 24 3.2.4 TAC穩定狀態之C0 25 3.2.5 給藥體重(dosing weight,DW)定義 25 3.2.6 TAC劑量校正C0(dose normalized C0,dnC0)定義 25 3.2.7 TAC納入分析之時間點(data collection) 25 3.2.8其它檢驗數據(laboratory data)之採檢日期 26 3.2.9併用藥品(concurrent medication)定義 26 3.2.10 TAC血中濃度檢驗方法 27 3.2.11 Genotyping方法 27 3.2.12其它定義 27 3.2.13統計分析 28 第四章、研究結果 31 4.1 病人篩選流程 31 4.2 病人人口學資料 31 4.3 TAC劑量與血中濃度變化 31 4.4 免疫抑制劑與併用藥品 32 4.5 病人基因型分布 33 4.6 生化檢驗值的變化 33 4.7 臨床因素與基因多型性單變項分析 34 4.7.1 移植手術出院前 34 4.7.2 移植後3個月 35 4.7.3 移植後6個月 35 4.7.4 CYP3A5表現者與不表現者基因多型性單變項分析 36 4.8 多變項分析 37 4.8.1 移植手術出院前 37 4.8.2 移植後3個月 37 4.8.3 移植後6個月 38 4.9 CYP3A5表現者與不表現者比較 39 4.9.1 移植手術出院前 39 4.9.2 移植後3個月 39 4.9.3 移植後6個月 40 4.10 免疫抑制劑組合分析 40 4.10.1 MPS vs. EVL 40 4.10.2 MMF vs. EVL 41 4.10.3 MMF/MPS vs. EVL 42 4.10.4 MPS vs. MMF 43 4.10.5 MMF/MPS user vs. non-user 44 第五章、討論 45 5.1 性別 45 5.2 年齡 46 5.3 類固醇每日劑量 47 5.4 MMF/MPS 48 5.5 T-bil/D-bil 49 5.6 Hb/Hct 50 5.7 基因多型性 50 5.7.1 CYP3A5*3 50 5.7.2 ABCB1 51 5.8 研究優勢與限制 52 第六章、結論 54 參考文獻 56 圖表 83 | - |
dc.language.iso | zh_TW | - |
dc.title | 基因多型性及臨床因素對腎臟移植病人tacrolimus血中濃度之影響 | zh_TW |
dc.title | The influence of genetic and clinical factors on tacrolimus blood concentration in renal transplant patients | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.coadvisor | 蔡孟昆;胡瑞恒 | zh_TW |
dc.contributor.coadvisor | Meng-Kun Tsai;Rey-Heng Hu | en |
dc.contributor.oralexamcommittee | 沈麗娟 | zh_TW |
dc.contributor.oralexamcommittee | Li-Jiuan Shen | en |
dc.subject.keyword | tacrolimus,腎臟移植,藥品動態學,藥品交互作用,臨床因素,基因多型性, | zh_TW |
dc.subject.keyword | tacrolimus,kidney transplantation,pharmacokinetics,drug interactions,clinical factors,genetic polymorphism, | en |
dc.relation.page | 172 | - |
dc.identifier.doi | 10.6342/NTU201802661 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-08-08 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 臨床藥學研究所 | - |
dc.date.embargo-lift | 2023-10-11 | - |
顯示於系所單位: | 臨床藥學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-2.pdf 目前未授權公開取用 | 3.45 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。