Impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese renal transplant recipients
10.3969/j.issn.1001-1978.2016.11.021
- VernacularTitle:CYP3 A5基因型对中国肾移植术后患者体内他克莫司缓释剂型药动学参数的影响
- Author:
Pan CHEN
;
Qian FU
;
Jingjie LI
;
Pingping SUN
;
Rongrong DENG
;
Jun LI
;
Xiaoman LIU
;
Hongyang WANG
;
Min HUANG
;
Xiao CHEN
;
Changxi WANG
- Publication Type:Journal Article
- Keywords:
tacrolimus;
modified release;
renal trans-plantation;
CYP3 A5;
pharmacokinetics;
genetic poly-morphism;
immunosuppressant
- From:
Chinese Pharmacological Bulletin
2016;32(11):1592-1595
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.
