Details

Autor(en) / Beteiligte

• 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

Titel

Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients

Ist Teil von

• Acta pharmacologica Sinica, 2015-05, Vol.36 (5), p.644-650

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 UGTIA9 -1818T〉C, 1399C〉T, -118T9/10, -440C〉T, -331T〉C, UGT2B7 IVS1＋985A〉G, 211G〉T, -900A〉G, UGT1A8 518C〉G and UGTIA7 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 AUCo_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 AUCo_12 h of the patients with the UGTIA 7 622CC and UGTIA9 -440CT/-331TC genotypes, respectively, was significantly higher than that of the patients with 622T homozygotes and -440C/-331T homozygotes. Furthermore, the genotypes UGTIA9 -1818T〉C and UGTIA8 518C〉G were associated with a low dose-adjusted MPAG AUCo_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.