Paper - WANFANG MED ONLINE

You Position: Home > Paper

Population pharmacokinetics of tacrolimus in Chinese renal transplant patients

( views:338, downloads:188 )

Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 7

DOI:: 10.3321/j.issn:0513-4870.2008.07.005

Key Word:: 他克莫司;群体药物动力学;非线性混合效应模型;肾移植

Abstract：本研究旨在考察口服他克莫司(tacrolimus)在中国肾移植患者中的群体药物动力学特征并探讨群体药物动力学参数和相关因素间的关系.研究中回顾性搜集了58例肾移植患者的802份他克莫司稳态全血样本资料.患者随机分为模型建立组(41例)和模型验证组(17例).用非线性混合效应模型(NONMEM)程序中的一级评估法(first-order estimation, FO)对模型建立组的数据进行分析.计算清除率(CL/F)、表观分布容积(V/F)的群体典型值,定量评价人口统计学指标、生化指标和合并用药等固定效应因素对药物动力学参数的影响.单室一级吸收和消除模型能够较好地拟合数据.最终模型包含了移植术后时间(POD)、红细胞压积(HCT)、谷草转氨酶(AST)、合并使用佩尔地平(NICA)和地尔硫草(DIL)等对CL/F的影响.用模型验证组数据进行验证的结果表明观测值和模型预测值之间没有明显的偏倚,模型的稳定性和准确度较好.CL/F和V/F的群体典型值分别为21.7L·h-1和241L;相应的个体间变异分别为41.6%和49.7%.观测值与预测值之间的残差SD为2.19μg·L-1.本文建立的模型可以为临床他克莫司剂量选择提供一定参考.

Reference

[1]夏东亚,蒋苓,邱实,等.ELISA法监测肾移植患者他克莫司全血浓度448例次[J].2004,(2).
[2]张弨,翟所迪,马潞林.用NONMEM法估算肾移植患者术后口服普乐可复的群体药代动力学特征[J].2005,(3).
[3]Zahir H,McCaughan G,Nelson A,etc.Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients.[J].2005,27(4).
[4]Kazuko Nagase,Kazuhide Iwasaki,Katsuko Nozaki,etc.Distribution and Protein Binding of FK506, a Potent Immunosuppressive Macrolide Lactone, in Human Blood and Its Uptake by Erythrocytes[J].1994,46(2).
[5]Hannoun L,Touitou Y,Hulot JS,etc.Population pharmacokinetics of tacrolimus in full liver transplant patients: modelling of the post-operative clearance.[J].2005,61(5).
[6]W J, Jusko,W, Piekoszewski,G B, Klintmalm,etc.Pharmacokinetics of tacrolimus in liver transplant patients.[J].1995,57.
[7]Clement-De-Clety S,Lykavieris L,Schafer A,etc.Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients.[J].1998,23(3).
[8]Uemoto S,Masuda S,Ogura Y,etc.Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients.[J].2006,80(4).
[9]Lam AY,Hebert MF.Diltiazem increases tacrolimus concentrations.[J].1999,33(6).
[10]Charles BG,Staatz CE,Taylor PJ,etc.Population pharmacokinetics of tacrolimus in children who receive cut-down or full liver transplants.[J].2001,72(6).
[11].Japanese study of FK 506 on kidney transplantation: the benefit of monitoring the whole blood FK 506 concentration. Japanese FK 506 Study Group.[J].1991,23.
[12]L B, Sheiner,S L, Beal.Some suggestions for measuring predictive performance.[J].1981,9(4).
[13]W J, Jusko,R, D'Ambrosio.Monitoring FK 506 concentrations in plasma and whole blood.[J].1991,23.
[14]Hideari Ihara,Denji Shinkuma,Yasuji Ichikawa,etc.Intra- and Interindividual Variation in the Pharmacokinetics of Tacrolimus (Fk506) in Kidney Transplant Recipients-Importance of Trough Level as a Practical Indicator[J].1995,2(3).
[15]R, Venkataramanan,A, Jain,V S, Warty,etc.Pharmacokinetics of FK 506 in transplant patients.[J].1991,23.
[16]Willis C,Tett SE,Staatz CE,etc.Population pharmacokinetics of tacrolimus in adult kidney transplant recipients.[J].2002,72(6).
[17]Hashimoto Y,Shimomura M,Inui K,etc.Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats.[J].1998,15(10).
[18]Ishibashi T,Oguma T,Yano Y.Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients.[J].2003,56(2).
[19]William J. Jusko,Wojciech Piekoszewski,Goran B. Klintmalm,etc.Pharmacokinetics of tacrolimus in liver transplant patients[J].1995,57(3).
[20]Lechat P,Urien S,Farinotti R,etc.Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patients.[J].2007,64(6).
[21]Lim SG,Lee KH,Ho PC,etc.Population pharmacokinetics of tacrolimus in whole blood and plasma in asian liver transplant patients.[J].2006,45(1).
[22]Inui K,Fukatsu S,Yano I,etc.Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation.[J].2001,57(6).
[23]Santos Buelga-D,Otero MJ,Serrano J,etc.Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data.[J].1999,20(5).
[24]Raman Venkataramanan,Arun Swaminathan,Tata Prasad,etc.Clinical Pharmacokinetics of Tacrolimus[J].1995,29(6).
[25]J E, Kay,E, Sampare-Kwateng,F, Geraghty,etc.Uptake of FK 506 by lymphocytes and erythrocytes.[J].1991,23.
[26]W, Piekoszewski,W J, Jusko.Plasma protein binding of tacrolimus in humans.[J].1993,82(3).
[27]Sam WJ,Aw M,Quak SH,etc.Population pharmacokinetics of tacrolimus in Asian paediatric liver transplant patients.[J].2000,50(6).
[28]Moller A,Undre NA,Schafer A,etc.The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects.[J].1999,27(6).
[29]Lu W,Gao J,Li D,etc.Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients.[J].2007,32(5).
[30]T, Goto,T, Kino,H, Hatanaka,etc.FK 506: historical perspectives.[J].1991,23.