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- Title
Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients.
- Authors
Xie, Xiao-chun; Li, Jun; Wang, Hong-yang; Li, Hong-liang; Liu, Jing; Fu, Qian; Huang, Jia-wen; Zhu, Chen; Zhong, Guo-ping; Wang, Xue-ding; Sun, Ping-ping; Huang, Min; Wang, Chang-xi; Li, Jia-li
- Abstract
Aim:To evaluate the effects of UDP-glucuronosyltransferases (UGTs) polymorphisms on the pharmacokinetics of the immunosuppressant mycophenolate mofetil (MMF) in Chinese renal transplant recipients.Methods:A total of 127 renal transplant patients receiving MMF were genotyped for polymorphisms in UGT1A9 −1818T>C, I399C>T, −118T9/10, −440C>T, −331T>C, UGT2B7 IVS1+985A>G, 211G>T, −900A>G, UGT1A8 518C>G and UGT1A7 622T>C. The plasma concentrations of the MMF active moiety mycophenolic acid (MPA) and main metabolite 7-O-MPA-glucuronide (MPAG) were analyzed using HPLC. Univariate and multivariate analyses were used to assess the effects of UGT-related gene polymorphisms on MPA pharmacokinetics.Results:The dose-adjusted MPA AUC0-12 h of the patients with the UGT2B7 IVS1+985AG genotype was 48% higher than that of the patients with the IVS1+985AA genotype, which could explain 11.2% of the inter-individual variation in MPA pharmacokinetics. The dose-adjusted MPAG AUC0-12 h of the patients with the UGT1A7 622CC and UGT1A9 −440CT/−331TC genotypes, respectively, was significantly higher than that of the patients with 622T homozygotes and −440C/−331T homozygotes. Furthermore, the genotypes UGT1A9 −1818T>C and UGT1A8 518C>G were associated with a low dose-adjusted MPAG AUC0-12 h.Conclusion:The UGT2B7 11+985A>G genotype is associated with the pharmacokinetics of MPA in Chinese renal transplant patients, which demonstrates the usefulness of this SNP for individualizing MMF dosing.
- Subjects
GLUCURONOSYLTRANSFERASE; MYCOPHENOLIC acid; PHARMACOKINETICS; KIDNEY transplant patients; CHINESE people; POLYMORPHISM (Crystallography); IMMUNOSUPPRESSIVE agents
- Publication
Acta Pharmacologica Sinica, 2015, Vol 36, Issue 5, p644
- ISSN
1671-4083
- Publication type
Article
- DOI
10.1038/aps.2015.7