AIM: To clarify whether Mycophenolic acid(MPA) or its metabolite AcMPAG can cause gastrointestinal disturbances, and to explore the effect of UGT2B7 SNP 211G>T on the pharmacokinetic of AcMPAG. METHODS: Twenty-four...AIM: To clarify whether Mycophenolic acid(MPA) or its metabolite AcMPAG can cause gastrointestinal disturbances, and to explore the effect of UGT2B7 SNP 211G>T on the pharmacokinetic of AcMPAG. METHODS: Twenty-four renal transplant patients were enrolled in this study. Pharmacokinetic study was performed on day 14 after transplantation and symptoms were recorded on the same day. Multiple blood samples were collected before dosing and 0.5,1,1.5,2,4,6,8,10 and 12 hours after morning dosing. Plasma concentrations of MPA, MPAG and AcMPAG were detected by HPLC. Genotype of UGT2B7 211G>T was determined using PCR-RFLP method. RESULTS: No significant difference was observed between patients with and without side effects for AUC(0-12) of MPA and MPAG. The values of AUC(0-12)/dose of MPA, MPAG and AcMPAG were (39.7±12.3), (1063.7±646.5) and (10.2±3.0) ng·h·mL-1·mg-1 in TT genotype group and (42.0±20.0),(1466.5±683.3) and (20.7±5.6) ng·h·mL-1·mg-1 in GG genotype group, respectively. The ratio of AUCAcMPAG(0-12)/AUCCMPA(0-12), which was used to describe the change of UGT2B7 enzyme activity, was 0.49±0.20,0.34±0.26 and 0.28±0.14 in recipients with 211GG, GT and TT genotype, respectively(P<0.05). CONCLUSION: There was no significant differences in pharmacokinetics of MPA and its metabolites between side effect group and non-side effect group. It seems that the polymorphism 211G>T in the UGT2B7 gene results in the reduction of enzyme acitivity.展开更多
文摘AIM: To clarify whether Mycophenolic acid(MPA) or its metabolite AcMPAG can cause gastrointestinal disturbances, and to explore the effect of UGT2B7 SNP 211G>T on the pharmacokinetic of AcMPAG. METHODS: Twenty-four renal transplant patients were enrolled in this study. Pharmacokinetic study was performed on day 14 after transplantation and symptoms were recorded on the same day. Multiple blood samples were collected before dosing and 0.5,1,1.5,2,4,6,8,10 and 12 hours after morning dosing. Plasma concentrations of MPA, MPAG and AcMPAG were detected by HPLC. Genotype of UGT2B7 211G>T was determined using PCR-RFLP method. RESULTS: No significant difference was observed between patients with and without side effects for AUC(0-12) of MPA and MPAG. The values of AUC(0-12)/dose of MPA, MPAG and AcMPAG were (39.7±12.3), (1063.7±646.5) and (10.2±3.0) ng·h·mL-1·mg-1 in TT genotype group and (42.0±20.0),(1466.5±683.3) and (20.7±5.6) ng·h·mL-1·mg-1 in GG genotype group, respectively. The ratio of AUCAcMPAG(0-12)/AUCCMPA(0-12), which was used to describe the change of UGT2B7 enzyme activity, was 0.49±0.20,0.34±0.26 and 0.28±0.14 in recipients with 211GG, GT and TT genotype, respectively(P<0.05). CONCLUSION: There was no significant differences in pharmacokinetics of MPA and its metabolites between side effect group and non-side effect group. It seems that the polymorphism 211G>T in the UGT2B7 gene results in the reduction of enzyme acitivity.
基金supported by grants from the Major State Basic Research Development Program of China("973"Program)(2011CB510000)the National Natural Science Foundation of China(81130021,81171198,81200870,81000542)
