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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李伯皇(Po-Huang Lee) | |
dc.contributor.author | Chih-Yuan Lee | en |
dc.contributor.author | 李志元 | zh_TW |
dc.date.accessioned | 2021-06-13T02:00:59Z | - |
dc.date.available | 2008-07-01 | |
dc.date.copyright | 2007-07-20 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-09 | |
dc.identifier.citation | Allison AC, Hovi T, Watts RW, Webster AD. Immunological observations on patients with Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation. Lancet 1975; 2(7946):1179-1183.
Arns W, Cibrik DM, Walker RG, Mourad G, Budde K, Mueller EA, Vincenti F. Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature. Transplantation 2006; 82(8):1004-1012. Atcheson BA, Taylor PJ, Mudge DW, Johnson DW, Hawley CM, Campbell SB, Isbel NM, Pillans PI, Tett SE. Mycophenolic acid pharmacokinetics and related outcomes early after renal transplant. British Journal of Clinical Pharmacology 2005; 59(3):271-280. Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after singledose oral and intravenous administration. Journal of Clinical Pharmacology 1996; 36(4):315-324. Bullingham RE, Nicholls A, Hale M. Pharmacokinetics of mycophenolate mofetil (RS61443): a short review. Transplantation Proceedings 1996; 28(2):925-929. Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clinical Pharmacokinetics 1998; 34(6):429-455. Cox VC, Ensom MH. Mycophenolate mofetil for solid organ transplantation: does the evidence support the need for clinical pharmacokinetic monitoring? Therapeutic Drug Monitoring 2003; 25(2):137-157. Eugui EM, Almquist SJ, Muller CD, Allison AC. Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. Scandinavian Journal of Immunology 1991; 33(2):161-173. Eugui EM, Mirkovich A, Allison AC. Lymphocyte-selective antiproliferative and immunosuppressive effects of mycophenolic acid in mice. Scandinavian Journal of Immunology 1991; 33(2):175-183. European Mycophenolate Mofetil Cooperative Study Group. Placebocontrolled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 1995; 345(8961):1321-1325. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosinedeaminase deficiency in two patients with severely impaired cellular immunity. Lancet 1972; 2(7786):1067-1069. Glander P, Hambach P, Braun K-P, et al. Pre-Transplant Inosine Monophosphate Dehydrogenase Activity is Associated with Clinical Outcome After Renal Transplantation. American Journal of Transplantation 2004; 4(12):2045-2051. Kiberd BA, Lawen J, Fraser AD, Keough-Ryan T, Belitsky P. Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation. American Journal of Transplantation 2004; 4(7):1079-1083. Kuss R and Bourget P. An Illustrated History of Organ Transplantation: Sandoz, 1992. Pawinski T, Hale M, Korecka M, et al. Limited Sampling Strategy for the Estimation of Mycophenolic Acid Area under the Curve in Adult Renal Transplant Patients Treated with Concomitant Tacrolimus. Clinical Biochemistry 2002; 48(9):1497-1504. Picard N, Premaud A, Rousseau A, et al. A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients. British Journal of Clinical Pharmacology 2006; 62(4):477-484. Pillans PI, Rigby RJ, Kubler P, Willis C, Salm P, Tett SE, Taylor PJ. A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients. Clinical Biochemistry 2001; 34(1):77-81. Saitoh H, Kobayashi M, Oda M, Nakasato K, Kobayashi M, Tadano K. Characterization of intestinal absorption and enterohepatic circulation of mycophenolic Acid and its 7-O-glucuronide in rats. Drug Metabolism and Pharmacokinetics 2006; 21(5):406-413. Sakaeda T. MDR1 genotype-related pharmacokinetics: fact or fiction? Drug Metabolism and Pharmacokinetics 2005; 20(6):391-414. Shaw LM, Korecka M, Venkataramanan R, Goldberg L, Bloom R, Brayman KL. Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies. American Journal of Transplantation 2003; 3(5):534-542. Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60(3):225-232. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61(7):1029-1037. van Gelder T. Mycophenolate mofetil: how to further improve using an already successful drug? American Journal of Transplantation 2005; 5(2):199-200. van Gelder T, Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet JP, Hene RJ, Verpooten GA, Navarro MT, Hale MD, Nicholls AJ. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation 1999; 68(2):261-266. Westley IS, Brogan LR, Morris RG, Evans AM, Sallustio BC. Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: effect of cyclosporine. Drug Metabolism And Disposition 2006; 34(2):261-266. Yatscoff RW, LeGatt D, Keenan R, Chackowsky P. Blood distribution of rapamycin. Transplantation 1993; 56:1202-1206. Yu ZC, Zhou PJ, Da X, et al. Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal transplant patients. British Journal of Clinical Pharmacology 2006; 62(4):446-452. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30318 | - |
dc.description.abstract | Mycophenolate mofetil (MMF) 是一種免疫抑制劑,經常和其他抗排斥藥物合併使用在接受器官移植的病患上,預防移植器官排斥反應的發生。
Mycophenolic acid (MPA)是病患服用MMF之後,經過代謝在人體內所產生具有活性的代謝產物。MPA 主要作用在抑制purine 合成的de novo pathway,藉此抑制淋巴球的分裂來達成抑制免疫反應的目的。 一些研究指出血液中MPA 的濃度和急性排斥的發生率有相關。 而血液中MPA的濃度同時也和感染的發生率以及藥物毒性有相關。 目前在臨床上,MMF的使用是根據病患可以忍受的劑量,給予病患 口服一天兩次、 一次0.5~1g的MMF,而沒有監測血液中藥物濃度。 因此,在合併其他抗排斥藥物使用的情況下,不知道血液中MPA的濃度是否會因為併用其他藥物而改變。本研究的目的在於比較服用不同免疫抑制劑,包括cyclosporine、 tacrolimus 或是sirolimus (沒有合併使用calcineurin inhibitor) 的腎臟移植病患,血液中MPA濃度的是否不同,以作為臨床上調整藥物劑量的參考。 本研究收集從2000年1月到2006年1月在台大醫院外科進行腎臟移 植,移植腎的功能穩定達六個月以上的病患。所有病患皆非B或C型肝炎的帶原者。根據服用的免疫抑制藥的種類將病患分為三組,包括cyclosporine 、 tacrolimus或是sirolimus三組。 除了上述藥物以外,病人服用的免疫抑制劑還包括口服類固醇以及每天兩次、每次0.5~1g的MMF。 從這些腎臟移植的病患採集服藥前、 服藥後半小時、 以及服藥後兩小時的血液並測量血清中MPA的濃度。 這些病患的腎臟功能、服藥前血液中cyclosporine、 tacrolimus或是sirolimus的藥物濃度皆定期每個月於門診追蹤六個月以上。血清中MPA濃度的測量是使用Emit® 2000Mycophenolic Acid Assay (Syva company, Dade Behring Inc., Cupertino, CA,USA)。 我們發現服用的MMF劑量明顯影響服用MMF後半小時血清中MPA 濃度(p=0.005, ANCOVA),而相對之下體重對於服用MMF後半小時血清中MPA濃度較無相關(p=0.697, ANCOVA)。因此,之後的MPA濃度比較我們都使用MMF藥物每日劑量校正後服藥後MPA濃度(dose-normalized MPA concentration) 作比較。在已經收集的三組個案sirolimus,tacrolimus 以及cyclosporine 裡,cyclosporine 組的藥物劑量校正後服藥後半小時(C0.5h) MPA 濃度 (4+2.11 mg/L)明顯低於sirolimus 組(13.93+9 mg/L; P=0.004)以及tacrolimus 組(11.55+6.3 mg/L;P=0.034, multiple regression)。也就是在服用MMF的腎臟移植受贈者,如果同時服用cyclosporine會比同時服用tacrolimus或是sirolimus有較低的服藥後半小時MPA 濃度。 | zh_TW |
dc.description.abstract | Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is used in combination with other immunosuppressants for the prevention of rejection after solid organ transplantation. MPA, the active metabolite of mycophenolate mofetil, acts by inhibiting the de novo pathway of purine synthesis. Several studies have demonstrated a relationship between mycophenolic acid exposure and the incidence of acute rejection(van Gelder
1999; Pillans 2001; Kiberd 2004). The exposure to mycophenolic acid was also significantly related to infections and hematological toxicity(Atcheson 2005). In renal transplant recipients, MMF is currently administered at a dose of 1 to 2g daily without monitor of the drug level. The objectives of this study were to compare the concentration of mycophenolic acid between patients receiving mycophenolate mofetil and either cyclosporine, tacrolimus or sirolimus and to investigate the factors that influenced serum MPA level. Methods: This study recruited patients who received renal transplantation in National Taiwan University Hospital between Jan. 2000 and Jan. 2006 with stable post-transplantation renal function for more then 6 months. All patients were neither hepatitis B nor hepatitis C carrier. Patients were divided into 3 groups according to their immunosuppressant regimens, either cyclosporine (n=7), tacrolimus (n=15) or sirolimus (without calcineurin inhibitor, n=24). Besides calcineurin inhibitor or sirolimus, all patients also received steroid and 0.5g to 1g of MMF twice daily by oral route. Patients who took both calcineurin inhibitor and sirolimus were not included in this study. Blood samples were collected from these patients for measurement of pre-dose (C0), 0.5 hour post-dose (C0.5) and 2 hour post-dose (C2) MPA concentration. Renal function and trough serum level of cyclosporine, tacrolimus or sirolimus of these patients were followed monthly for at least 6 months. Emit® 2000 Mycophenolic Acid Assay (Syva Company, Dade Behring Inc., Cupertino, CA, USA) was used to measure plasma MPA concentration. The MPA concentration and estimated AUC were compared among the 3 groups. Results: We collected data from 46 patients in total, 24 patients in sirolimus group, 15 in tacrolimus group and 7 in cyclosporine group. First of all, we wanted to know whether body weight or dosage of MMF would influence MPA concentration in plasma. In this study, 0.5 hour post-dose MPA concentration was significantly correlated with the dosage of MMF (p=0.005, ANCOVA) but not the body weight (p=0.697, ANCOVA). Therefore, we used daily MMF dose-normalized MPA concentration for further comparison. The MMF dosenormalized trough MAP concentration and 2 hour post-dose MPA concentration were not significantly different among the three groups. The MMF dose-normalized 0.5 hour post-dose MPA concentration in the cyclosporine group (4+2.11mg/L) was significantly lower than that in the sirolimus group (13.93+9 mg/L; P=0.004) or tacrolimus group (11.55+6.3 mg/L;P=0.034, multiple regression). Conclusion: We demonstrated that 0.5 hour post-dose MPA concentration was significantly correlated with the daily dosage of MMF but not the body weight. The MMF dose-normalized 0.5 hour post-dose MPA concentration in the cyclosporine group was significantly lower than that in the sirolimus group or tacrolimus group. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T02:00:59Z (GMT). No. of bitstreams: 1 ntu-96-P92421005-1.pdf: 1157560 bytes, checksum: 511dd2441b2d6770ff3a9fca53549f61 (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 論文口試委員審定書 .....................................1
臺灣大學碩士論文授權書....................................2 誌謝......................................................3 中文摘要..................................................4 英文摘要..................................................6 目錄......................................................9 第一章、序論.............................................12 研究背景.................................................12 研究主題及其重要性.......................................17 研究目的.................................................18 第二章、研究方法與材料...................................20 病患個案的收集...........................................20 測量MPA濃度時間點的決定..................................20 檢體收集.................................................20 MPA濃度的測量............................................21 統計方法.................................................21 第三章、結果.............................................23 病患基本資料.............................................23 三組之間MPA濃度比較......................................23 單變項及多變項分析.......................................23 體重以及MMF藥物劑量對於MPA濃度的影響.....................24 每日MMF劑量校正MPA 濃度後單變項及多變項分析..............25 腎臟功能對於MPA濃度的影響................................26 免疫抑制劑血中濃度對於MPA濃度的影響......................26 血中白蛋白(albumin)濃度對於MPA濃度的影響.................26 每日MMF劑量校正後血清中MPA濃度在三組間的差異.............27 第四章、討論.............................................28 第五章、展望.............................................32 第六章、表...............................................34 表一、本研究收集個案的基本資料...........................34 表二、服用MMF劑量以及各組血清中MPA濃度...................35 表三、單變項及多變項分析影響服藥後半小時MPA濃度的因素....36 表四、依服用免疫抑制劑分組,使用單變項分析探討病患體重對於服藥後半小時MPA濃度的影響................................37 表五、 依服用免疫抑制劑分組,使用單變項分析探討服用MMF劑量對於服藥後半小時MPA濃度的影響............................38 表六、 單變項及多變項分析影響MMF劑量校正後服藥後半小時MPA濃 度的因素.................................................39 表七、各組MMF每日劑量校正後血清中MPA濃度(Daily MMF dosenormalized MPA concentration)........................40 第七章、圖.......................................................41 圖一、服藥後半小時血清中MPA濃度和體重的相關性............41 圖二、服用MMF劑量和服藥後半小時血清中MPA濃度的相關性.....42 圖三之一、血清中creatinine濃度和服用MMF劑量校正後服藥後半小時血清中MPA濃度(MMF dose-normalized MPA concentration)的相關性.....................................................43 圖三之二、血清中creatinine濃度和服用MMF劑量校正後服藥後半小時血清中MPA濃度(MMF dose-normalized MPA concentration)的相關性:分組回歸...........................................44 圖四、血清中免疫抑制劑濃度和服用MMF劑量校正後服藥後半小時血清中MPA濃度(MMF dose-normalized MPA concentration)的相關性.......................................................45 圖五、MMF每日劑量校正後服藥後半小時MPA濃度和血清中的白蛋白濃度的相關性.............................................46 圖六、各組MMF每日劑量校正後血清中MPA濃度(Daily MMF dosenormalized MPA concentration)的比較..................47 參考文獻.................................................48 附錄.....................................................52 附錄一、臨床試驗計畫書...................................52 附錄二、臨床試驗受試者說明及同意書.......................55 | |
dc.language.iso | zh-TW | |
dc.title | 腎臟移植病患服用Mycophenolate Mofetil同時合併服用Cyclosporine、 Tacrolimus 或是 Sirolimus對於血清中Mycophenolic Acid藥物濃度的影響 | zh_TW |
dc.title | The Effect of Cyclosporine、Tacrolimus and Sirolimus on the Concentration of Mycophenolic Acid in Renal Transplant Recipients Taking Mycophenolate Mofetil | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 賴明坤,江伯倫,李伯璋 | |
dc.subject.keyword | 腎臟移植, | zh_TW |
dc.subject.keyword | Renal transplantation,Mycophenolate mofetil,Mycophenolic acid,cyclosporine,tacrolimus,sirolimus, | en |
dc.relation.page | 59 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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