Correlation Of Polymorphism Of UGT1A1 Genetic Polymorphisms And The Interindividual Variations Of Pharmacokinetics Parameters Of Slymarin

Objective:To study the correlation between UGT1A1 polymorphisms and the interindividual variations of pharmacokinetics of silymarin.Methods:Genotyping of UGT1A1*6(211G>A) and UGT1A1*28 (TATA box TA repeats) were determined by pyrosequencing sequenator in 75 male healthy volunteers.16 male healthy volunteers, grouped by genotype, received a single oral dose of 560 mg silymarin. Venous blood samples of 5 mL were drawn from forearm vein into EDTA tubes before(0h) and at 0.25,0.5,0.75,1,1.5,2,3,4,6,8,12h, respectively, after silymarin administration. Plasma was separated, and determined by HPLC method. The pharmacokinetics of silymarin was analyzed, Then the effect of UGT1A1 polymorphisms on pharmacokinetics of silymarin was analyzed.Results:1. UGT1A1*6 was completely linkage with UGT1A1*28, in male healthy volunteers, the frequency of UGT1A1*6 and UGT1A1*28 are both 10.7%, there was no subjects with (TA)7/(TA)7 and 211 A/A was found in this ivestigation.2. The mean AUC0-12,AUC0-∞,Cmax,t1/2å'ŒCmax of silymarin in subjects with (TA)6/(TA)7 and 211G/A genotype is 1437.5±681.7 ng·h·ml-1.1467.9±657.0ng·h·ml-1,630.6±291.7 ng·ml-1,2.9±2.3h,1.6±0.7 h respectively, which are all higher than those subjects with (TA)6/(TA)6 and 211G/G genotype (1089.9±366.7 ng·h·ml-1,1120.5±350.8 ng·h·ml-1,427.0±130.1 ng·ml-1,2.2±1.7h,1.4±0.3h), where only Cmax is with significant meaning. CL/F of (TA)6/(TA)6 and 211G/G genotype carriers is higher than (TA)6/(TA)7 and 211G/A genotype carriers, where not significant meaning.Conclusion:UGT1A1*6 and UGT1A1*28 are significant correlated with the Cmax of silymarin in healthy volunteers. There was no significant correlation between the polymorphism of UGT1A1 and the AUC0-12,AUC0-∞,Cmax,t1/2 and CL/F of silymarin in healthy volunteers.