Effect Of UGT1A9 And UGT2B7 Polymorphisms On Pharmacokinetics Of Mycophenolic Acid In Vivo

OBJECTIVE:To investigate the frequency of UGT1A9-440C/T,UGT1A9 I399C/T and UGT2B7 211G/T in health Han of Chinese,and whether they are in linkage disequilibrium in Chinese.Then,use MPA as probe,we research on the UGT1A9-440C/T,UGT1A9 I399C/T and UGT2B7 211G/T function important.METHOD:Genotypes were determined using the PCR-RFLP method. Suitable subjects have been selected out.All subjects received 1500mg MMF tablet on first day morning after fasting over night.,blood samples were draw in 0h,0.25h,0.5h,0.75h,1h,1.5,2h,4h,6h,8h,10h,12h,24h,48h,72h after taking the drug and the plasma concentrations of MMF were measured by HPLC.RESULT:The frequence of UGT1A9-440C/T,UGT1A9 I399C/T & UGT2B7 211G/T in health Hart of Chinese is 3.63%,55.02%, 13.21%,respectively.Comparison between different genotypes of the pharmacokinetic parameters,211GG/-440CC/399CC genotype compared with 211GG/-440CT/399CC genotype,MPA Cmax(48451±15022 than 72689±21716;p=0.02) were statistically significant differences;MPA AUC0-6h(11.11±0.35 than 11.54±0.24;p=0.02) were significantly different.211GG/-440CC/399CC Genotype subjects and 211TT/-440CT/ 399CC Genotype subjects compared,MPAG Cmax(43725±19353 than 63345±27658;p=0.04) there is significant difference;MPA AUC6-72h (11.04±0.32 than 11.61±0.64;p=0.01) were statistically significant differences;MPAG AUC6-72h(12.77±0.22 than the 13.20±0.54;p=0.03) there were significant difference statistically The MPA and MPAG of Cmax,AUC6-72h and Tmax in subjects with 211GG/-440CC/399TT genotype were not significant differences. CONCLUSION:Our results suggest that UGT1A9-440C/T,UGT2B7 211G/T SNP might play an important role in the pharmacokinetics of MPA and MPAG,it should be taken into consider in the clinical use.The UGT1A9 variant I399C/T did not seem to affect the pharmacokinetics of MPA and MPAG.