請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48372
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林淑文 | |
dc.contributor.author | Yu-Ting Huang | en |
dc.contributor.author | 黃玉婷 | zh_TW |
dc.date.accessioned | 2021-06-15T06:54:18Z | - |
dc.date.available | 2016-03-03 | |
dc.date.copyright | 2011-03-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-02-11 | |
dc.identifier.citation | 1.Prod Info VFEND(R) IV injection , oral tablets, suspension, 2008. US Food and Drug Administration.
2.Weiss J, ten Hoevel MM, Burhenne J, et al. CYP2C19 Genotype Is a Major Factor Contributing to the Highly Variable Pharmacokinetics of Voriconazole. The Journal of Clinical Pharmacology 2009;49:196-204. 3.Morrison A, Levy R. Toward individualized pharmaceutical care of East Asains: the value of genetic testing for polumorphisms in drug-metabolizing genes. Pharmacogenomics 2004;5(6):673-89. 4.Liou Y-H, Lin C-T, Wu Y-J, Wu LS-H. The high prevalence of the poor and ultrarapid metabolite alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 in Taiwanese population. Journal of Human Genetics 2006;51:857-63. 5.Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases 2008;46:327-60. 6.Bruggemann RJ, Donnelly JP, Aarnoutse RE, et al. Therapeutic drug monitoring of voriconazole. Ther Drug Monit 2008;30(4):402-11. 7.Pauw BD, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-21. 8.Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis 2008;47:674-83. 9.Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med, 2002; 347(6):408-15. 10.Cornely OA, Maertens J, Bresnik M, et al. Liposomal Amphotericin B as Initial Therapy for Invasive Mold Infection: A Randomized Trial Comparing a High–Loading Dose Regimen with Standard Dosing (AmBiLoad Trial). Clinical Infectious Diseases 2007;44:1289-97. 11.Pagano L, Caira M, Valentini CG, Posteraro B, Fianchi L. Current therapeutic approaches to fungal infections in immunocompromised hematological patients. Blood Reviews 2010;24:51-61. 12.Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006;91(8) 1068-75. 13.Mahfouz T, Anaissie E. Prevention of fungal infections in the immunocompromised host. Curr Opin Investig Drugs 2003;4:974-90. 14.Pagano L, Caira M, Anna C, Massimo O, Martino B, Giorgina S. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. haematologica 2010;95:644-50. 15.Parody R, Martino R, Sanchez F, Subira M, Hidalgo A, Sierra J. Predicting survival in adults with invasive aspergillosis during therapy for hematological malignancies or after hematopoietic stem cell transplantation: Single-center analysis and validation of the Seattle, French, and Strasbourg prognostic indexes. Am J Hematol 2009;84:571-78. 16.Gallien S, Fournier S, Porcher R, et al. Therapeutic outcome and prognostic factors of invasive aspergillosis in an infectious disease department: a review of 34 cases. Infecion 2008;36:533-38. 17.Nivoix Y, Velten M, Letscher-Bru V, Moghaddam A, Natarajan-Ame S, Fohrer C. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin Infect Dis 2008;47. 18.Sanati H, Belanger P, Fratti R, Ghannoum M. A New Triazole, Voriconazole (UK-109,496), Blocks Sterol Biosynthesis in Candida albicans and Candida krusei. Antimicrobial Agents and Chemotherapy 1997;41:2492-96. 19.Manavathu EK, Cutright JL, Chandrasekar PH. Organism-Dependent Fungicidal Activities of Azoles. Antimicrobial Agents and Chemotherapy 1998;42:3018-21. 20.Carrillo AJ, Guarro J. In Vitro Activities of Four Novel Triazoles against Scedosporium spp. Antimicrobial Agents and Chemotherapy 2001;45:2151-3. 21.Barry AL, Brown SD. In Vitro Studies of Two Triazole Antifungal Agents (Voriconazole [UK-109,496] and Fluconazole) against Candida Species. Antimicrobial Agents and Chemotherapy 1996;40:1948-49. 22.Clancy CJ, Nguyen MH. In vitro efficacy and fungicidal activity of voriconazole against Aspergillus and Fusarium species. Eur J Clin Microbiol Infect Dis 1998;17:573-5 23.Johnson LB, Kauffman CA. Voriconazole A New Triazole Antifungal Agent. Clin Infect Dis 2003;36:630-7. 24.Cuenca-Estrella M, Ruiz-Díez B, Martínez-Suárez JV, L AMJ, Rodríguez-Tudela. Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. Journal of Antimicrobial Chemotherapy 1999;43:149-51. 25.Gomez-Lopez A, Cuenca-Estrella M, Monzon A, Rodriquez-Tudela J. In Vitro Susceptibility of Clinical Isolates of Zygomycota to Anphotericin B, Flucytosine, Itraconazole and Voriconazole. Journal of Antimicrobial Chemotherapy 2001;48:919-21. 26.Kontoyiannis DP, Lionakis MS, Lewis RE. Zygomycosis in a tertiary care cancer center in the era of Aspergillus active antifungal therapy a case control observational study of 27 recent cases. J Infect Dis 2005;191:1350-60. 27.Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet 2006;45 (7): 649-63. 28.Andes D, Marchillo K, Stamstad T, Conklin R. In Vivo Pharmacokinetics and Pharmacodynamics of a New Triazole, Voriconazole, in a Murine Candidiasis Model. Antimicrobial Agents and Chemotherapy 2003;47:3165-9. 29.Messer SA. Initial results from a longitudinal international surveillance programme for anidulafungin (2003). Journal of Antimicrobial Chemotherapy 2004;54:1051-6. 30.Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi. Journal of Clinical Microbiology 2003;41:3623-6. 31.Purkins L, Wood N, Kleinermans D, Greenhalgh K, Nichols D. Effect of food on the pharmacokinetics of multiple-dose oral voriconazole. British Journal of Clinical Pharmacology 2003;56:17-23. 32.Lutsar I, Roffey S, Troke P. Voriconazole Concentrations in the Cerebrospinal Fluid and Brain Tissue of Guinea Pigs and Immunocompromised Patients. Clin Infect Dis 2003;37:728-32. 33.Purkins L, Wood N, Ghahramani P, Greenhalgh K, Allen MJ, Kleinermans D. Pharmacokinetics and Safety of Voriconazole following Intravenous- to Oral-Dose Escalation Regimens. Antimicrobial Agents and Chemotherapy 2002;46:2546-53. 34.Hyland R, Jones BC, Smith DA. Identification of the cytochrome p450 enzymes involved in the N-oxidation of voriconazole. Drug Metabolism and Disposition 2003;31 540-47. 35.Leveque D, Nivoix Y, Jehl F, Herbrecht R. Clinical pharmacokinetics of voriconazole. International Journal of Antimicrobial Agents 2006;27:274-84. 36.行政院衛生署. 黴飛-西藥、醫療器材、含藥化妝品許可證查詢。( Accessed 12/28, 2010, at http://203.65.100.151/DO8180A.asp.). 37.Walsh TJ, Karlsson MO, Driscoll T, et al. Pharmacokinetics and Safety of Intravenous Voriconazole in Children after Single- or Multiple-Dose Administration. Antimicrobial Agents and Chemotherapy 2004;48:2166-72. 38.EPARs for authorised medicinal products for human use - Vfend. Accessed 3 January 2011 Available at http://wwwemeaeuropaeu/humandocs/Humans/EPAR/vfend/vfendhtm 39.Voriconazole in DRUGDEX® System [intranet database]. . Version 51 Greenwood Village, Colo: Thomson Healthcare. 40.Imataki O, Ohnishi H, Kitanaka A, Kubota Y, Ishida T, Tanaka T. Visual disturbance comorbid with hallucination caused by voriconazole in the Japanese population. International Journal of Hematology 2008;88:3-6. 41.Zonios DI, Gea‐Banacloche J, Childs R, Bennett JE. Hallucinations during Voriconazole Therapy. Clinical Infectious Diseases 2008;47:e7-e10. 42.FDA Antiviral Drugs Advisory Committee. Briefing Document for voriconazole. US Food and Drug Administration 2001. 43.Bartlett JG, Auwaerter PG, Pham PA. Diagnosis and Treatement of Infectious Diseases Johns Hopkins ABX Guide 2010 second edition: Jones & Bartlett Learing;Appendix III Drug-To-Drug Interaction Tables:842-4. 44.Howard A, tHoffman J, Sheth A. Clinical application of voriconazole concentrations in the treatment of invasive aspergillosis. The Annals of Pharmacotherapy 2008;42:1859-64. 45.Goodwin ML, Drew RH. Antifungal serum concentration monitoring: an update. Journal of Antimicrobial Chemotherapy 2008;61:17-25. 46.Denning DW, Ribaud P, Milpied N. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002;34:563-71. 47.Trifilio S, Pennick G, Pi J, et al. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer 2007;109:1532-5. 48.Smith J, Andes D. Therapeutic drug monitoring of antifungals: pharmacokinetic and pharmacodynamic considerations. Ther Drug Monit 2008;30:167-72. 49.Trifilio S, Ortiz R, Pennick G, et al. Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplantation 2005;35:509-13. 50.Smith J, Safdar N, Knasinski V, et al. Voriconazole therapeutic drug monitoring. Antimicrobial Agents and Chemotherapy 2006;50(4):1570-2. 51.Imhof A, Schaer DJ, Schanz U, Schwarz U. Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring. Swiss Mes Wkly 2006;136:739-42. 52.Tan K. Investigation of the Potential Relationships Between Plasma Voriconazole Concentrations and Visual Adverse Events or Liver Function Test Abnormalities. The Journal of Clinical Pharmacology 2006;46:235-43. 53.Pascual A, Thierry C, Saskia B, Thierry B, Jacques B, Oscar M. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 2008;46:201-11. 54.Okuda T, Okuda A, Watanabe N, Takao M, Takayanagi K. Retrospective serological tests for determining the optimal blood concentration of voriconazole for treating fungal infection. Yakugaku Zasshi 2008;128:1811-8. 55.Matsumoto K, Ikawa K, Abematsu K, et al. Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes. Int J Antimicrob Agents 2009;34(1):91-4. 56.Ueda K, Nannya Y, Kumano K, et al. Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders. Int J Hematol 2009;89:592-9. 57.Miyakis S, van Hal SJ, Ray J, Marriott D. Voriconazole concentrations and outcome of invasive fungal infections. Clin Microbiol Infec 2010;16:927-33. 58.Pascual A, Nieth V, Calandra T, et al. Variability of Voriconazole Plasma Levels Measured by New High-Performance Liquid Chromatography and Bioassay Methods. Antimicrobial Agents and Chemotherapy 2006;51:137-43. 59.Lin S-C, Lin S-W, Chen J-M, Kuo C-H. Using sweeping-micellar electrokinetic chromatography to determine voriconazole in patient plasma. Talanta 2010;82:653-9. 60.Acute myeloid leukemia in National Comprehensive Cancer Network. ( Accessed 23, November, 2010, at: http://wwwnccnorg/professionals/physician_gls/PDF/amlpdf ). 61.Chronic myeloid leukemia in National Comprehensive Cancer Network ( Accessed 23, November, 2010, at: http://wwwnccnorg/professionals/physician_gls/PDF/cmlpdf ). 62.Non-Hogkin's lymphoms in National Comprehensive Cancer Network. ( Accessed 23, November, 2010, at: http://wwwnccnorg/professionals/physician_gls/PDF/nhlpdf ). 63.Multiple myeloma in National Comprehensive Cancer Network. ( Accessed 23, November, 2010, at: http://wwwnccnorg/professionals/physician_gls/PDF/mmpdf ). 64.Hogkin's lymphoms in National Comprehensive Cancer Network. ( Accessed 23, November, 2010, at: http://wwwnccnorg/professionals/physician_gls/PDF/hlpdf ). 65.National Cancer Institute. Serious adverse events definitions: National Cancer Institute onlone guidelines 2006. ( Accessed 11, November, 2010, at http://ctepcancergov/reporting/ctchtml ). 66.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45. 67.Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008;14(44):6774-85. 68.Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidermiol 1993;Vol.46:1323-30. 69.Tatro DS. Drug Interaction Facts TM . The Authority on Drig Interactions2010 St Louis: Wolters Kluwer Health. 70.曾郁茹。. 某醫學中心voriconazole使用現狀之回溯性研究[碩士論文];指導教授:沈麗娟、林淑文;. 臨床藥學所,台灣大學; 2010. 71.von Mach MA, Burhenne J, Weilemann LS. Vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients. BMC Clinical Pharmacology 2006;6:1-6. 72.Pfaller MA, Messer SA, Hollis RJ, Jones RN. Antifungal Activities of Posaconazole, Ravuconazole, and Voriconazole Compared to Those of Itraconazole and Amphotericin B against 239 Clinical Isolates of Aspergillus spp. and Other Filamentous Fungi: Report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrobial Agents and Chemotherapy 2002;46:1032-7. 73.Vehreschild JJ, Böhme A, Reichert D, et al. Treatment of invasive fungal infections in clinical practice: a multi-centre survey on customary dosing, treatment indications, efficacy and safety of voriconazole. International Journal of Hematology 2008;87:126-31. 74.den Hollander J. G. Incidence of voriconazole hepatotoxicity during intravenous and oral treatment for invasive fungal infections. Journal of Antimicrobial Chemotherapy 2006;57:1248-50. 75.Potoski BA, Brown J. The safety of voriconazole. Clin Infect Dis 2002;35:1273-75. 76.Pascual A, Bolay O, Oscar M. Monitoring of voriconazole blood levels: 1 year experence at an university hospital. 45th Intersience conference on Antimicrobial Agents and Chemotherapy;Washington DC 2005. 77.Cyclosporine in DRUGDEX® System [intranet database]. . Version 51 Greenwood Village, Colo: Thomson Healthcare. 78.Tacrolimus in DRUGDEX® System [intranet database]. . Version 51 Greenwood Village, Colo: Thomson Healthcare. 79.Amphotericin B in DRUGDEX® System [intranet database]. . Version 51 Greenwood Village, Colo: Thomson Healthcare. 80.Mori T, Aisa Y, Kato J, Nakamura Y, Ikeda Y, Okamoto S. Drug interaction between voriconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplantation 2009;44:371-4. 81.Wood N, Tan K, Purkins L, et al. Effect of omeprazole on the steady-state pharmacokinetics of voriconazole. British Journal of Clinical Pharmacology 2003;56:56-61. 82.Blume H, Donath F, Warnke Ae, Schug BS. Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors. Drug Safety 2006;29 (9):769-84. 83.Ogawa R, Echizen H. Drug-Drug Interaction Profiles of Proton Pump Inhibitors. Clin Pharmacokinet 2010; 49 (8):509-33. 84.Larson AM, Kaplan MM, Bonis PAL. Drugs and the liver: Patterns of drug-induced liver injury. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48372 | - |
dc.description.abstract | 背景 :
Voriconazole為新一代三唑類廣效抗黴菌藥品,主要用來治療侵入性麴菌感染,本身經由肝臟酵素CYP2C19所代謝,具有非線性藥品動態學特性,易造成病人voriconazole血中濃度個體差異性大;亞洲族群約有20-30%為CYP2C19慢代謝者,這類病人有較高比例發生與濃度相關之不良反應,如肝毒性、視聽力幻覺等。目前臺灣尚未有voriconazole療劑監測相關資料建立,本研究以前瞻性收案使用voriconazole的病人,藉由量測voriconazole血中濃度,評估病人臨床療效以及不良反應與voriconazole血中濃度間之關聯性。 研究目的 : 分析收案期間voriconazole處方型態,包括使用劑量、途徑、適應症、併用藥品、治療天數等,以及評估voriconazole血中波谷濃度(trough concentration)、波峰濃度(peak concentration)與臨床療效、不良反應之相關性。 研究方法 : 本研究於2009年3月1日至2010年6月30日間,在國立臺灣大學醫學院附設醫院前瞻性收案門診或住院使用voriconazole治療的病人,經由病人簽署受試者同意書,等病人使用voriconazole 5-7天達穩定血中濃度狀態後,服用(或注射)早晨的劑量之前量測血中波谷濃度(trough concentration);等到服用口服錠劑2小時後(或注射結束後1小時),量測血中波峰濃度(peak concentration),測量儀器為高效能液相層析儀系統(HPLC)以UV偵測吸收波長,並提供醫療團隊血中濃度結果報告,視病人臨床反應調整voriconazole劑量或更換其他抗黴菌藥品。 於收案期間記錄病人基本資料、實驗室檢驗值、voriconazole處方型態等,並觀察療程中有無發生不良反應或藥品交互作用,其中不良反應以Naranjo scale評估與voriconazole之相關性;於病人結束voriconazole療程後,請感染專科醫師評估療程適應症與治療反應,若治療結果為治癒或部分治癒則定義為治療成功。 統計方法以χ2 test、Student’s t test、Mann-Whitney U Test比較兩組樣本間之差異,以及使用ANOVA進行三組樣本之比較。以多變項羅吉斯迴歸模式以及運用廣義估計等式(generalized estimating equations,GEE)校正病人有重覆量測資料如voriconazole濃度、肝腎功能指數等,以評估voriconazole血中濃度是否為影響療效與不良反應重要相關因子,另外使用複廣義相加模式分析(generalized additive model,GAM) 找出療效與不良反應的血中濃度分界點。 研究結果 本研究總共收案68人,有效樣本為40人,共有53次療程。病人中位數年齡為46歲( 18-85歲),男性與女性比例19 : 21,潛在疾病以血液疾病為主,占有82.5%。收案期間之療劑監測資料,共收集波峰濃度有42 筆與波谷濃度有103筆,病人量測voriconazole次數中位數為2次(1-11),共有11位病人量測次數達3次以上,這些病人自己所有量測波谷濃度中,濃度差距可達2.5-33.7倍,代表病人自體間濃度差異性很大;另外,第一次監測血中濃度中有12位病人(30%)是落於文獻建議範圍之外(1 - 6 mcg/mL),且病人濃度個體差異性大,差距達1-93倍;靜脈注射維持劑量平均值為7.28 ± 1.76 mg/kg/day,波峰濃度中位數為4.74 mcg/mL(1.16-15 mcg/mL),波谷濃度中位數為3.0 mcg/mL(0.33-18.6 mcg/mL);而口服劑量平均值為8.62 ± 3.27 mg/kg/day,口服波峰濃度中位數為4.24 mcg/mL(0.48-8.83 mcg/mL),波谷濃度中位數為2.81 mcg/mL(0.2-10.97 mcg/mL)。 適應症評估方面,有78%療程為確定或極為可能侵入性黴菌感染,感染部位與致病黴菌以肺部及麴菌感染為主。治療反應有43.4%為治療成功案例,完全治癒、部分治癒各占一半比例;56.6%治療失敗案例中,評估結果以疾病惡化占最多數(28.3%),而治療反應評估為死亡者占17.0%,其中只有5.7%因為侵入性黴菌感染而死亡;治療天數中位數為45天(5-355)。 收案期間所發生與voriconazole相關之不良反應中,最常見為肝毒性事件(30.2%),表現型態以膽汁鬱積類型占多數(43.8%),其次為視覺障礙與幻覺情形各占有17.0%與7.5%,而這些不良反應開始作用時間(onset)在開始使用voriconazole後約10天左右即發生。藥品交互作用方面,最常見併用藥品alprazolam(20.8%),其次為cyclosporine(15.1%),大致上併用藥品有參考仿單與文獻調整劑量與監測相關數值。 影響voriconazole治療反應最重要相關因子為潛在血液疾病狀態(OR= 7.29,95% CI : 1.37-38.82),血中濃度方面如波谷濃度、療程中位數濃度等在控制其他相關因子後與治療反應呈正相關,但未達統計顯著意義。不良反應方面,voriconazole血中波谷濃度為影響肝毒性重要相關因子,在控制其他相關因子後波谷濃度OR = 1.20(95% CI: 1.01-1.42),並且以GAM發現毒性濃度分界點為4.5 mcg/mL,而病人療程前ALP基準值為影響肝毒性最重要因子,OR=2.27 ( 95% CI: 1.03-5.02 );在幻覺不良反應分析中,voriconazole波峰與波谷濃度皆為重要相關因子(波谷濃度: OR=1.54,95% CI: 1.23-1.94;波峰濃度: OR=1.43,95% CI:1.12-1.82);反觀另一神經毒性視覺障礙,即使在控制其他相關因子,不論是voriconazole波峰或波谷濃度皆無達統計顯著意義(波峰濃度:OR=0.93,95% CI: 0.70-1.25;波谷濃度: OR=1.00,95% CI: 0.81-1.23)。 結論 本研究中病人以血液疾病族群為主,有22.5%為B型肝炎帶原者,而voriconazole主要用來治療侵入性肺部麴菌感染,治療反應有43.4%為治療成功案例,不良反應以膽汁鬱積型之肝毒性占多數。voriconazole血中濃度病人個體間與自體間差異性大,血中濃度為影響不良反應之肝毒性與幻覺的重要相關因子,其中肝毒性濃度分界點為4.5 mcg/mL;在治療反應方面,voriconazole血中濃度呈現正相關但未達統計顯著意義,而潛在血液疾病狀態則為影響治療反應最重要因素。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:54:18Z (GMT). No. of bitstreams: 1 ntu-100-R97451003-1.pdf: 2256355 bytes, checksum: e8493049aa2365a2e6bae43efba06e30 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 致謝………………………………………………………………… i
中文摘要…………………………………………………………… ii Abstract…………………………………………………………… v 目錄……………………………………………………………… viii 圖目錄……………………………………………………………… x 表目錄………………………………………………………………xi 縮寫表…………………………………………………………… xiv 第一章 緒論…………………………………………………… 1 第二章 文獻探討……………………………………………… 2 2.1 侵入性黴菌感染…………………………………… 2 2.2 Voriconazole簡介………………………………… 8 2.3 療劑監測……………………………………………… 21 第三章 研究目的……………………………………………… 26 第四章 研究方法…………………………………………… 27 4.1 研究架構…………………………………………… 27 4.2 收案流程……………………………………………… 28 4.3 研究對象、地點……………………………………… 29 4.4 納入及排除條件……………………………………… 29 4.5 相關資料收集………………………………………… 29 4.6 濃度測量方法………………………………………… 31 4.7 侵入性黴菌感染適應症與臨床反應評估…………… 32 4.8 不良反應評估………………………………………… 38 4.9 肝毒性評估…………………………………………… 39 4.10 藥品交互作用………………………………………… 42 4.11 統計方法…………………………………………… 44 第五章 研究結果……………………………………………… 45 5.1 收案病人流程………………………………………… 45 5.2 描述性統計…………………………………………… 46 5.3 統計檢定……………………………………………… 69 第六章 討論…………………………………………………… 84 6.1 病人族群……………………………………………… 84 6.2 適應症……………………………………………… 84 6.3 劑量與濃度…………………………………………… 85 6.4 療劑監測探討………………………………………… 87 6.5 治療反應…………………………………………… 89 6.6 不良反應…………………………………………… 90 6.7 藥品交互作用……………………………………… 94 6.8 療劑監測之臨床考量………………………………… 95 6.9 研究限制……………………………………………… 96 6.10 未來展望…………………………………………………… 97 第七章 結論………………………………………………… 98 參考文獻………………………………………………………… 98 | |
dc.language.iso | zh-TW | |
dc.title | 侵入性黴菌感染使用voriconazole之療劑監測研究 | zh_TW |
dc.title | Therapeutic Drug Monitoring of Voriconazole in Patients with Invasive Fungal Infections | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-1 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 沈麗娟 | |
dc.contributor.oralexamcommittee | 張上淳,林慧玲,陳宜君 | |
dc.subject.keyword | voriconazole,侵入性黴菌感染,療劑監測,voriconazole血中濃度,治療反應,肝毒性, | zh_TW |
dc.subject.keyword | Voriconazole,invasive fungal infections,therapeutic drug monitoring,voriconazole plasma concentration,treatment response,liver toxicity, | en |
dc.relation.page | 106 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-02-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
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-100-1.pdf 目前未授權公開取用 | 2.2 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。