期刊
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
卷 69, 期 1, 页码 53-63出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00228-012-1296-4
关键词
Tacrolimus; Population pharmacokinetics; Pharmacogenetics; Kidney transplantation; Nonlinear mixed-effect modeling (NONMEM)
资金
- National Research Foundation of Korea (NRF)
- Korea government (MEST) [2011-0000354]
Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene encoding P-glycoprotein (ABCB1), on the PK parameters in adult Korean kidney transplant recipients. Clinical data were collected retrospectively for 400 days after the initiation of a tacrolimus-based immunosuppression therapy. Data from 2,788 trough blood samples obtained from 80 subjects were used to perform a population PK analysis with a nonlinear mixed-effect model (NONMEM). The estimated population mean values of clearance (CL/F) and volume of distribution (V/F) were 22.9 L/h and 716 L, respectively, and the k (a) was fixed to 4.5 h(-1). The CYP3A5 genotype, hematocrit level, and post-operative days were identified as the main covariates that influence CL/F, and body weight was found to have a significant effect on V/F. Other covariates, including ABCB1 genotype, corticosteroid dosage, sex, and other clinical data, did not contribute to the pharmacokinetics of tacrolimus. This tacrolimus population PK model will be a valuable tool in developing rational guidelines and provides a basis for individualized therapy after kidney transplantation in clinical settings of Korea.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据