北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第三临床医学院  > 期刊论文
学科主题: 临床医学
题名:
Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation
作者: Hu, Yong-Fang; Qiu, Wen; Liu, Zhao-Qian; Zhu, Li-Jun; Liu, Zhong-Qi; Tu, Jiang-Hua; Wang, Dan; Li, Zhi; He, Jun; Zhong, Gan-Ping; Zhou, Gan; Zhou, Hong-Hao
关键词: Chinese ; cyclosporine ; CYP3A4 ; CYP3A5 ; MDR1 (ABCB1) ; polymorphisms ; transplantation
刊名: CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
发表日期: 2006-11-01
DOI: 10.1111/j.1440-1681.2006.04492.x
卷: 33, 期:11, 页:1093-1098
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Physiology
研究领域[WOS]: Pharmacology & Pharmacy ; Physiology
关键词[WOS]: P-GLYCOPROTEIN ; KIDNEY-TRANSPLANTATION ; AFRICAN-AMERICAN ; HUMAN-LIVER ; TACROLIMUS ; EXPRESSION ; METABOLISM ; SEQUENCE ; DISPOSITION ; CDNA
英文摘要:

The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes.

The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients.

One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3 and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose-adjusted trough blood concentrations (C-0) were determined and compared among the different genotype groups.

The frequency of the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose-adjusted C-0 in CYP3A5*1/*1 genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal-Wallis test). Accordingly, cyclosporine dose-adjusted C-0 was larger in CYP3A5 non-expressors than expressors in the first week after renal transplantation. In addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but significantly lower dose-adjusted C-0 compared with heterozygotes (n = 58): 17.7 (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann-Whitney U-test).

In conclusion, the present study shows that genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3 variant genotype require a low dose of cyclosporine to reach target levels compared with those with the CYP3A5*1 allele.

语种: 英语
WOS记录号: WOS:000241241700014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67779
Appears in Collections:北京大学第三临床医学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Hosp 3, Beijing 100871, Peoples R China
2.Cent S Univ, Inst Clin Pharmacol, Pharmacogenet Res Inst, Changsha 410078, Peoples R China
3.Cent S Univ, Affiliated Xiangya Hosp 3, Changsha, Hunan, Peoples R China
4.Second Affiliated Hosp, Lanzhou Med Coll, Lanzhou, Gansu, Peoples R China

Recommended Citation:
Hu, Yong-Fang,Qiu, Wen,Liu, Zhao-Qian,et al. Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,2006,33(11):1093-1098.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Hu, Yong-Fang]'s Articles
[Qiu, Wen]'s Articles
[Liu, Zhao-Qian]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Hu, Yong-Fang]‘s Articles
[Qiu, Wen]‘s Articles
[Liu, Zhao-Qian]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace