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学科主题: 临床医学
题名:
Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis
作者: Shi, Wei-Long; Tang, Hui-Lin; Zhai, Suo-Di
刊名: PLOS ONE
发表日期: 2015-06-03
DOI: 10.1371/journal.pone.0127995
卷: 10, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: SOLID-ORGAN TRANSPLANTATION ; ACUTE REJECTION RATES ; CYTOCHROME-P450 3A ; CALCINEURIN INHIBITORS ; DOSE REQUIREMENTS ; CYP3A5 ; LIVER ; PHARMACOGENETICS ; CYCLOSPORINE ; DISPOSITION
英文摘要:

Background and Objective

The association between the CYP3A4*1B single nucleotide polymorphism (SNP) and tacrolimus pharmacokinetics in different studies is controversial. Therefore, a meta-analysis was employed to evaluate the correlation between the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics at different post-transplantation times in adult renal transplant recipients.

Methods

Studies evaluating the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics were retrieved through a systematical search of Embase, PubMed, the Cochrane Library, ClinicalTrials.gov and three Chinese literature databases (up to Sept. 2014). The pharmacokinetic parameters (weight-adjusted tacrolimus daily dose and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio) were extracted, and the meta-analysis was performed using Stata 12.1.

Results

Seven studies (involving 1182 adult renal transplant recipients) were included in this meta-analysis. For the weight-adjusted tacrolimus daily dose, in all included renal transplant recipients (European & Indian populations), CYP3A4*1/*1 recipients required a significantly lower weight-adjusted tacrolimus daily dose than did CYP3A4* 1B carriers at 7 days (WMD -0.048; 95% CI -0.083 similar to -0.014), 6 months (WMD -0.058; 95% CI -0.081 similar to -0.036) and 12 months (WMD -0.061; 95% CI -0.096 similar to -0.027) post-transplantation. In light of the heterogeneity, the analysis was repeated after removing the only study in an Indian population, and CYP3A4*1/*1 European recipients (mostly Caucasian) required a lower weight-adjusted tacrolimus daily dose within the first year post-transplantation. The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C-0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 similar to 82.789) and 12 months (WMD 62.219; 95% CI 14.218 similar to 110.221) post-transplantation. When the only study in an Indian population was removed to examine European recipients (mostly Caucasian), the significant difference persisted at 1 month, 6 months and 12 months post-transplantation.

Conclusion

Based on our meta-analysis, the CYP3A4*1B genetic polymorphism affects tacrolimus dose requirements and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio within the first year post-transplantation in adult renal transplant recipients, especially in European recipients (mostly Caucasian).

语种: 英语
WOS记录号: WOS:000355700700084
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58949
Appears in Collections:北京大学第三临床医学院_药剂科_期刊论文

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作者单位: Peking Univ, Hosp 3, Dept Pharm, Beijing 100871, Peoples R China

Recommended Citation:
Shi, Wei-Long,Tang, Hui-Lin,Zhai, Suo-Di. Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis[J]. PLOS ONE,2015,10(6).
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