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Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers
Tang, Hui-Lin1; Xie, Hong-Guang2; Yao, Yao1; Hu, Yong-Fang1
关键词CYP3A5 immunosuppressant meta-analysis organ transplantation personalized medicine pharmacogenomics tacrolimus
刊名PHARMACOGENETICS AND GENOMICS
2011-11-01
DOI10.1097/FPC.0b013e32834a48ca
21期:11页:713-720
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
关键词[WOS]RENAL-TRANSPLANT RECIPIENTS ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SOLID-ORGAN TRANSPLANTATION ; MDR1 ABCB1 POLYMORPHISMS ; CALCINEURIN INHIBITORS ; CLINICAL PHARMACOKINETICS ; KIDNEY-TRANSPLANTATION ; GENETIC POLYMORPHISMS ; TROUGH CONCENTRATIONS ; ALLOGRAFT RECIPIENTS
英文摘要

Background CYP3A5 genetic polymorphisms contribute to marked interindividual differences in the metabolism of and response to tacrolimus in humans.

Objective This study was aimed to clarify the impact of the CYP3A5*3 variant on tacrolimus dose requirements and acute rejection rates in patients with organ transplantation.

Methods A literature search was performed up to August 2009 by using the Cochrane library, PubMed, Medline, and EMBase.

Results Twenty-three studies (a total of 1779 patients) were included in this meta-analysis. Eighteen studies (1443 patients) were involved in renal transplantation and five studies (336 patients) in liver transplantation. Results of meta-analysis demonstrated that, in renal transplant patients, despite the presence of significant heterogeneity, CYP3A5 expressers required higher mean tacrolimus daily doses by 0.045 mg/kg (95% confidence interval (CI), 0.033-0.056) than nonexpressers. Furthermore, sub-analysis of the time of posttransplantation showed that CYP3A5 expressers required higher daily doses than nonexpressers by 0.010, 0.084, 0.041, 0.037, and 0.044 mg/kg at week 2, and at month 1, 3, 6, and 12, respectively. Subset analysis of the ethnicity of organ recipients indicated that mean tacrolimus daily doses were 0.056, 0.037, and 0.077 mg/kg higher in CYP3A5 expressers than nonexpressers for white, Chinese, and Japanese patients, respectively. In contrast, for liver transplant patients, higher tacrolimus daily doses were required not only in CYP3A5 expressers of the organ donors than nonexpressers by 0.024 mg/kg (95% CI, 0.019-0.028), but also in CYP3A5 expresser of the organ recipients than nonexpresser by 0.012 mg/kg (95% CI, 0.005-0.018). However, a significant difference in the acute organ rejection rate was observed only at one month (odds ratio, 3.27; 95% CI, 1.57-6.81; P = 0.002).

Conclusion Tacrolimus daily dose requirements may vary with the presence of the CYP3A5*3 variant, ethnicity of the organ recipients, and the time of posttransplantation. In addition, the acute organ rejection rate may be higher in CYP3A5 expressers than nonexpressers over the first month after transplantation. Pharmacogenetics and Genomics 21:713-720 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

语种英语
所属项目编号81072705
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000296146400004
Citation statistics
Cited Times:43[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/400002259/62880
Collection北京大学第三临床医学院
作者单位1.Peking Univ, Hosp 3, Therapeut Drug Monitoring & Clin Toxicol Ctr, Beijing 100191, Peoples R China
2.Univ Calif San Francisco, UC Washington Ctr, Ctr Drug Dev Sci, Dept Bioengn & Therapeut Sci, Washington, DC USA
Recommended Citation
GB/T 7714
Tang, Hui-Lin,Xie, Hong-Guang,Yao, Yao,et al. Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers[J]. PHARMACOGENETICS AND GENOMICS,2011,21(11):713-720.
APA Tang, Hui-Lin,Xie, Hong-Guang,Yao, Yao,&Hu, Yong-Fang.(2011).Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers.PHARMACOGENETICS AND GENOMICS,21(11),713-720.
MLA Tang, Hui-Lin,et al."Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers".PHARMACOGENETICS AND GENOMICS 21.11(2011):713-720.
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