Effect of CYP3A5 and CYP3A4 on pharmacokinetics of Tacrolimus in renal transplantation recipients
10.3760/cma.j.issn.0254-1785.2012.04.008
- VernacularTitle:肾移植受者C YP3A5*3和CYP3A4*18B对他克莫司药动学的影响
- Author:
Ling LIN
;
Wenli SONG
;
Zhongyang SHEN
;
Yi ZHANG
- Publication Type:Journal Article
- Keywords:
Kidney transplantation;
Tacrolimus;
Pharmacokinetics;
Cytochrome P-450 CYP3A5;
Cytochrome P 450 CYP3A4;
Gene polymorphisms
- From:
Chinese Journal of Organ Transplantation
2012;33(4):220-224
- CountryChina
- Language:Chinese
-
Abstract:
Objective To retrospectively investigate the effects of CYP3A5 * 3,CYP3A4 * 18B and CYP3A5-CYP3A4 phenotype on the C0,D and C0/D of tacrolimus (Tac) in renal transplantation recipients.Methods The CYP3A5 * 3 and CYP3A4 * 18B genotypes of the 61 patients were detected by DNA direct sequencing,and the C0 was detected by ELISA.The differences of C0,D and C0/D on the day 14,and month 1,2 and 3 after transplantation were compared among different genotypes of recipients treated with Tac.Results The frequency of the CYP3A5 * 3 and CYP3A4 * 18B was 74.6％ and 26.2％ respectively.When the D of the recipients with CYP3A5 * 1 ( * 1/* 1 + * 1/* 3)was 1.3-1.6 times to theCYP3A5*3/*3,theC0 of *3/*3 group was 1.1-1.5 times to the * 1group,and the C0/D was 1.8 2.4 times to the CYP3A5 * 1.For CYP3A4,the D of CYP3A4 * 18B group ( * 1/* 18B+ * 18B/* 18B) was 1.2-1.5 times to the CYP3A5 * 1/* 1,but the C0 of 1/* 1was 1.2-1.4 times to the * 18B,the C0/D was 1.5-1.8 times to the * 18B.For the CYP3A5 CYP3A4 phenotype,the D of the recipients with AAAA was 1.3-1.7 times to the GG-GG,the C0 of GG-GG was 1.5-2 times to the AA-AA,the C0/D of the recipients with G@GG was 2.5-3 times to the AA-AA.In the recipients with C0/D above or below the median of C0/D,the distribution of CYP3A5,CYP3A4 and CYP3A5-CYP3A4 phenotypes was different significantly.Conclusion There is a significant correlation between the CYP3A5,CYP3A4 and pharmacokinetics of Tac.It's more powerful evaluating the CYP3A5-CYP3A4 phenotype rather than just one genotype of the recipients.So detecting the CYP3A5 * 3 and CYP3A4 * 18B genotypes prior to transplantation is meaningful for us to determine an appropriate initial and long-time dosage of Tac.
