IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients
Li, D.1; Lu, W.1; Zhu, J.-Y.1; Gao, J.1; Lou, Y.-Q.1; Zhang, G.-L.1
关键词Cyp3a5 Liver Polymorphism Population Pharmacokinetics Tacrolimus Transplantation
刊名JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
2007-10-01
32期:5页:505-515
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]NECROSIS-FACTOR-ALPHA ; RECIPIENTS ; DONOR ; INTERLEUKIN-10 ; FK506 ; CLEARANCE ; HAPLOTYPE ; ABCB1
英文摘要

Background and objective: Tacrolimus, an immunosuppressant widely used after liver transplantation, is characterized by a large inter-individual variability in its pharmacokinetics. The aim of this study was to perform population pharmacokinetic analysis of oral tacrolimus in liver transplant recipients and clarify the potential role of CYP3A5, MDR1 and IL-10 genetic polymorphisms in the variability of population pharmacokinetic parameters.

Methods: Tacrolimus blood concentration data (n = 1106) were collected from 104 full liver transplant patients and were analysed using a non-linear mixed-effects modelling program (NONMEM). The CYP3A5*3, MDR1 G2677T/A and C3435T genetic polymorphisms were determined using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. The IL-10 G-1082A variant was studied by allele-specific PCR method.

Results and discussion: The liver function in patients as indicated by the total bilirubin level (TBIL) and different CYP3A5*3 genotypes in donors (CYPD) and recipients (CYPR) were observed to influence tacrolimus pharmacokinetic parameter of apparent clearance (Cl/F). The final regression model can be expressed as Cl/F = 15.9 - 1.88 TBIL + 7.65 CYPD + 7.00 CYPR. The relative standard errors (%RSE) of the parameter estimation were lower than 30% and the residual variability of tacrolimus trough blood concentration was 2.81 ng/mL. No significant effect of MDR1 and IL-10 polymorphisms was observed on population pharmacokinetic parameter of tacrolimus within 175 days after liver transplantation.

Conclusion: The TBIL in patients and CYP3A5*3 genetic polymorphism in both donors and recipients contribute to the inter-individual variability of oral tacrolimus apparent clearance in Chinese adult liver transplant patients.

语种英语
WOS记录号WOS:000249450400013
Citation statistics
Cited Times:47[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50263
Collection北京大学基础医学院_药理学系
作者单位1.Beijing Univ, Ctr Hlth Sci, Basic Med Sch, Dept Pharmacol, Beijing 100083, Peoples R China
2.Beijing Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing, Peoples R China
3.Beijing Univ, Peoples Hosp, Liver Transplant Ctr, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Li, D.,Lu, W.,Zhu, J.-Y.,et al. Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients[J]. JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,2007,32(5):505-515.
APA Li, D.,Lu, W.,Zhu, J.-Y.,Gao, J.,Lou, Y.-Q.,&Zhang, G.-L..(2007).Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients.JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,32(5),505-515.
MLA Li, D.,et al."Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients".JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS 32.5(2007):505-515.
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