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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林君榮(Chun-Jung Lin) | |
dc.contributor.author | Ke-Wei Hsu | en |
dc.contributor.author | 許克瑋 | zh_TW |
dc.date.accessioned | 2021-06-15T11:44:23Z | - |
dc.date.available | 2019-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-12 | |
dc.identifier.citation | 1. Kristensen MB. Drug interactions and clinical pharmacokinetics. Clin Pharmacokinet. 1976; 1 (5): 351-372.
2. Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther. 2009; 85 (4): 434-438. 3. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995; 12 (3): 413-420. 4. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005; 22 (1): 11-23. 5. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009; 26 (9): 2039-2054. 6. Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev. 2016. 7. Mody GM, Cardiel MH. Challenges in the management of rheumatoid arthritis in developing countries. Best Pract Res Clin Rheumatol. 2008; 22 (4): 621-641. 8. Sacks JJ, Luo YH, Helmick CG. Prevalence of specific types of arthritis and other rheumatic conditions in the ambulatory health care system in the United States, 2001-2005. Arthritis Care Res (Hoboken). 2010; 62 (4): 460-464. 9. Butcher L. Rheumatoid arthritis: prevalence, economics, and implications for payers and purchasers. Biotechnol Healthc. 2008; 5 (2): 16-17. 10. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996; 14: 397-440. 11. Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 2008; 118 (11): 3537-3545. 12. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7 (6): 429-442. 13. Aitken AE, Morgan ET. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos. 2007; 35 (9): 1687-1693. 14. Dickmann LJ, Patel SK, Rock DA, Wienkers LC, Slatter JG. Effects of interleukin-6 (IL-6) and an anti-IL-6 monoclonal antibody on drug-metabolizing enzymes in human hepatocyte culture. Drug Metab Dispos. 2011; 39 (8): 1415-1422. 15. Dickmann LJ, Patel SK, Wienkers LC, Slatter JG. Effects of interleukin 1beta (IL-1beta) and IL-1beta/interleukin 6 (IL-6) combinations on drug metabolizing enzymes in human hepatocyte culture. Curr Drug Metab. 2012; 13 (7): 930-937. 16. Projean D, Dautrey S, Vu HK, Groblewski T, Brazier J-L, Ducharme J. Selective Downregulation of Hepatic Cytochrome P450 Expression and Activity in a Rat Model of Inflammatory Pain. Pharmaceutical Research. 2005; 22 (1): 62-70. 17. Uno S, Kawase A, Tsuji A, Tanino T, Iwaki M. Decreased Intestinal CYP3A and P-glycoproteîn Activities in Rats with Adjuvant Arthritis. Drug Metabolism and Pharmacokinetics. 2007; 22 (4): 313-321. 18. Sanada H, Sekimoto M, Kamoshita A, Degawa M. Changes in expression of hepatic cytochrome P450 subfamily enzymes during development of adjuvant-induced arthritis in rats. J Toxicol Sci. 2011; 36 (2): 181-190. 19. Uno S, Uraki M, Ito A, Shinozaki Y, Yamada A, Kawase A et al. Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant-induced arthritis rat. Biopharm Drug Dispos. 2009; 30 (1): 49-54. 20. Bishop H, Schneider RE, Welling PG. Plasma propranolol concentrations in rats with adjuvant-induced arthritis. Biopharm Drug Dispos. 1981; 2 (3): 291-297. 21. Ling S, Jamali F. Effect of early phase adjuvant arthritis on hepatic P450 enzymes and pharmacokinetics of verapamil: an alternative approach to the use of an animal model of inflammation for pharmacokinetic studies. Drug Metab Dispos. 2005; 33 (4): 579-586. 22. Verbeeck RK. Pathophysiologic factors affecting the pharmacokinetics of nonsteroidal antiinflammatory drugs. J Rheumatol Suppl. 1988; 17: 44-57. 23. Turesson C, Jarenros A, Jacobsson L. Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study. Ann Rheum Dis. 2004; 63 (8): 952-955. 24. Gabriel SE. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008; 121 (10 Suppl 1): S9-14. 25. Myasoedova E, Crowson CS, Nicola PJ, Maradit-Kremers H, Davis JM, Roger Vé L et al. The Impact of Rheumatoid Arthritis Disease Characteristics on Heart Failure. J Rheumatol. 2011; 38 (8): 1601-1606. 26. Sheng X, Murphy MJ, Macdonald TM, Wei L. Effectiveness of statins on total cholesterol and cardiovascular disease and all-cause mortality in osteoarthritis and rheumatoid arthritis. J Rheumatol. 2012; 39 (1): 32-40. 27. Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J. 2011; 13 (4): 519-547. 28. Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP et al. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999; 27 (3): 410-416. 29. Scripture CD, Pieper JA. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001; 40 (4): 263-281. 30. Kopplow K, Letschert K, Konig J, Walter B, Keppler D. Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol. 2005; 68 (4): 1031-1038. 31. Noe J, Portmann R, Brun ME, Funk C. Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007; 35 (8): 1308-1314. 32. Li J, Volpe DA, Wang Y, Zhang W, Bode C, Owen A et al. Use of transporter knockdown Caco-2 cells to investigate the in vitro efflux of statin drugs. Drug Metab Dispos. 2011; 39 (7): 1196-1202. 33. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA et al. Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000; 28 (11): 1369-1378. 34. Wu X, Whitfield LR, Stewart BH. Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter. Pharm Res. 2000; 17 (2): 209-215. 35. Chen C, Mireles RJ, Campbell SD, Lin J, Mills JB, Xu JJ et al. Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005; 33 (4): 537-546. 36. Grube M, Kock K, Oswald S, Draber K, Meissner K, Eckel L et al. Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin Pharmacol Ther. 2006; 80 (6): 607-620. 37. Kobayashi D, Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther. 2003; 306 (2): 703-708. 38. Watanabe T, Kusuhara H, Maeda K, Shitara Y, Sugiyama Y. Physiologically based pharmacokinetic modeling to predict transporter-mediated clearance and distribution of pravastatin in humans. J Pharmacol Exp Ther. 2009; 328 (2): 652-662. 39. Nakai D, Nakagomi R, Furuta Y, Tokui T, Abe T, Ikeda T et al. Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes. J Pharmacol Exp Ther. 2001; 297 (3): 861-867. 40. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP et al. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999; 274 (52): 37161-37168. 41. Kivisto KT, Grisk O, Hofmann U, Meissner K, Moritz KU, Ritter C et al. Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats. Drug Metab Dispos. 2005; 33 (11): 1593-1596. 42. Russo MW, Hoofnagle JH, Gu J, Fontana RJ, Barnhart H, Kleiner DE et al. The spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network. Hepatology. 2014; 60 (2): 679-686. 43. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016; 374 (7): 664-669. 44. Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother. 2002; 36 (2): 288-295. 45. Elsby R, Hilgendorf C, Fenner K. Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012; 92 (5): 584-598. 46. Schmitt C, Kuhn B, Zhang X, Kivitz AJ, Grange S. Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis. Clin Pharmacol Ther. 2011; 89 (5): 735-740. 47. Wagner S, Bindler J, Andriambeloson E. Animal models of collagen-induced arthritis. Curr Protoc Pharmacol. 2008; Chapter 5: Unit 5 51. 48. Watanabe T, Kusuhara H, Maeda K, Kanamaru H, Saito Y, Hu Z et al. Investigation of the rate-determining process in the hepatic elimination of HMG-CoA reductase inhibitors in rats and humans. Drug Metab Dispos. 2010; 38 (2): 215-222. 49. Watanabe T, Maeda K, Kondo T, Nakayama H, Horita S, Kusuhara H et al. Prediction of the hepatic and renal clearance of transporter substrates in rats using in vitro uptake experiments. Drug Metab Dispos. 2009; 37 (7): 1471-1479. 50. Jones HM, Houston JB. Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations. Drug Metab Dispos. 2004; 32 (9): 973-982. 51. Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007; 2 (5): 1269-1275. 52. Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006; 80 (4): 356-366. 53. Quion JA, Jones PH. Clinical pharmacokinetics of pravastatin. Clin Pharmacokinet. 1994; 27 (2): 94-103. 54. Higgins JW, Bao JQ, Ke AB, Manro JR, Fallon JK, Smith PC et al. Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein. Drug Metab Dispos. 2014; 42 (1): 182-192. 55. Pasanen MK, Fredrikson H, Neuvonen PJ, Niemi M. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2007; 82 (6): 726-733. 56. Pasternak RC, Smith SC, Jr., Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002; 40 (3): 567-572. 57. Jacobson TA. Statin safety: lessons from new drug applications for marketed statins. Am J Cardiol. 2006; 97 (8a): 44c-51c. 58. Mosshammer D, Schaeffeler E, Schwab M, Morike K. Mechanisms and assessment of statin-related muscular adverse effects. Br J Clin Pharmacol. 2014; 78 (3): 454-466. 59. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008; 359 (8): 789-799. 60. Lea AP, McTavish D. Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. Drugs. 1997; 53 (5): 828-847. 61. Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005; 4 (12): 977-987. 62. Palmer G, Chobaz V, Talabot-Ayer D, Taylor S, So A, Gabay C et al. Assessment of the efficacy of different statins in murine collagen-induced arthritis. Arthritis Rheum. 2004; 50 (12): 4051-4059. 63. 陳佳壕. 轉運蛋白與CYP酵素在藥物代謝上所扮演角色之探討. 博士論文. 2014. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49725 | - |
dc.description.abstract | 本研究的目的為探討在膠原蛋白誘發之關節炎 (CIA) 的疾病狀態下,對fluvastatin、atorvastatin與pravastatin於大鼠上的藥物動力學性質之影響。結果顯示,CIA大鼠口服fluvastatin與atorvastatin後,血中濃度與全身性的藥物暴露量均顯著高於control大鼠,而直接經由肝門靜脈給予fluvastatin與atorvastatin後也可以得到相似之結果。然而當pravastatin口服用於CIA大鼠後,其血中濃度與全身性的藥物暴露量與control大鼠相較下均沒有明顯的差異。而經由pravastatin直接經由肝門靜脈給藥後,亦無太大的差異性產生。從藥物動力學分析中推測fluvastatin與atorvastatin在CIA大鼠的血中濃度上升是因其擬似清除率下降所致。進一步發現fluvastatin與atorvastatin在CIA大鼠之肝細胞吸收清除率均有顯著下降,其中fluvastatin更在CIA大鼠之肝臟microsome代謝有受到抑制的現象。在肝臟及肌肉毒性方面,雖然fluvastatin與atorvastatin在CIA大鼠上有明顯的血中濃度增加,但血漿中肝臟毒性指標天門冬胺酸轉胺酶 (AST)、丙胺酸轉胺酶 (ALT) 與肌肉毒性指標肌酸激酶 (CK) 相較於control大鼠並無太大差異。而pravastatin的部分,由於在CIA大鼠與control大鼠上沒有明顯的血中濃度差異,因此在肝臟及肌肉毒性反應上亦沒有看到明顯的差異存在。 | zh_TW |
dc.description.abstract | The objective of the present study was to investigate the pharmacokinetic properties of fluvastatin, atorvastatin and pravastatin in collagen-induced arthritis (CIA) rats. When fluvastatin and atorvastatin were given orally, the plasma levels and systemic exposures of fluvastatin and atorvastatin were significantly higher in CIA rats than in control rats. Also, the results from portal vein injection were similar to those of oral doing of fluvastatin and atorvastatin. In contrast, there were no differences in the plasma level and systemic exposure of pravastatin between CIA and control rats. The pharmacokinetic analysis suggested that the increased plasma levels of fluvastatin and atorvastatin may be due to the decreased apparent clearances in CIA rats. Furthermore, the hepatic uptake clearances of fluvastatin and atorvastatin were significantly reduced, while the metabolism of fluvastatin was also slightly inhibited by hepatic microsome in CIA rats. However, the higher plasma levels of fluvastatin and atorvastatin in CIA rats did not cause a significant increase in the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), and CK (creatine kinase), compared with control rats. In the part of pravastatin, there were also no differences in hepatotoxicity (as measured for AST and ALT) and myotoxicity (as measured for CK) because of the similar plasma levels in CIA and control rats. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:44:23Z (GMT). No. of bitstreams: 1 ntu-105-R03423013-1.pdf: 2290720 bytes, checksum: dc27e91f3e9d8571492e5cc57425ee7e (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii Abstract iii 中文摘要 iv 目錄 v 圖目錄 vii 表目錄 viii 第一章 緒論.. 1 第二章 研究目的 9 第三章 實驗材料 10 3.1 膠原蛋白誘發之關節炎大鼠動物模式之建立 10 3.2 Statins在CIA與control大鼠上之藥物動力學試驗 10 3.3 Statins的樣品濃度檢測 11 3.4 Statins的毒性試驗 12 3.5 Statins在CIA與control大鼠上經肝門靜脈給藥之肝灌流試驗 12 3.6 Statins在CIA與control大鼠之肝細胞吸收試驗 13 3.7 Statins在CIA與control大鼠肝臟microsome之代謝試驗 16 第四章 實驗方法 18 4.1 膠原蛋白誘發之關節炎大鼠動物模式之建立 18 4.2 Statins在CIA與control大鼠上口服給藥之藥物動力學與毒性試驗 18 4.3 Statins在CIA與control大鼠上經肝門靜脈給藥之肝灌流試驗 19 4.4 Statins的血漿與膽汁中之濃度分析 19 4.5 Statins的肝臟與肌肉毒性試驗 20 4.6 Statins在CIA與control大鼠之肝細胞吸收試驗 20 4.7 Statins在CIA與control大鼠肝臟microsome之代謝試驗 23 4.8 實驗數據分析 24 第五章 實驗結果 29 5.1 評估膠原蛋白誘導之關節炎大鼠動物模式 29 5.2 Fluvastatin在CIA與control大鼠上之藥物動力學與毒性試驗 29 5.3 Fluvastatin在CIA與control大鼠上之肝灌流試驗 30 5.4 Atorvastatin在CIA與control大鼠上之藥物動力學與毒性試驗 30 5.5 Atorvastatin在CIA與control大鼠上之肝灌流試驗 31 5.6 Pravastatin在CIA與control大鼠上之藥物動力學與毒性試驗 31 5.7 Pravastatin在CIA與control大鼠上之肝灌流試驗 32 5.8 Statins在CIA與control大鼠之肝細胞吸收試驗 32 5.9 Statins在CIA與control大鼠肝臟microsome之代謝試驗 32 第六章 結果討論 43 第七章 結論 48 第八章 參考文獻 49 | |
dc.language.iso | zh-TW | |
dc.title | Fluvastatin、atorvastatin及pravastatin於膠原蛋白誘發之關節炎大鼠上藥物動力學性質之探討 | zh_TW |
dc.title | The pharmacokinetics of fluvastatin, atorvastatin and pravastatin in collagen-induced arthritis rat model | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鮑力恆(Li-Heng Pao),何蘊芳(Yun-Fang Ho) | |
dc.subject.keyword | 膠原蛋白誘發之關節炎,fluvastatin,atorvastatin,pravastatin,藥物動力學, | zh_TW |
dc.subject.keyword | collagen-induced arthritis (CIA),fluvastatin,atorvastatin,pravastatin,pharmacokinetics, | en |
dc.relation.page | 55 | |
dc.identifier.doi | 10.6342/NTU201602467 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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