Prediction of in vivo drug clearance from in vitro data. II: Potential inter-ethnic differences

摘要: Potential differences in drug clearance between Japanese and Caucasians were investigated by integrating data on demography, liver size, the abundance of major cytochromes P450 vitro metabolic parameters. Eleven drugs (alprazolam, caffeine, chlorzoxazone, cyclosporine, midazolam, omeprazole, sildenafil, tolbutamide, triazolam, S-warfarin zolpidem) fulfilled entry criteria study (i.e. necessary metabolism available values had been reported both Japanese). Values relevant biological variables obtained from literature, predictions made using Simcyp Population-Based ADME Simulator. The ratios observed oral (CLp.o.) compared with ranged 0.6 to 2.8 (integrating 82 sources). CLp.o. for alprazolam, caffeine zolpidem not statistically different Caucasian (p>0.05), whereas those chorzoxazone, tolbutamide triazolam higher (p<0.05), sildenafil (p<0.05). values, predicted data, within 3-fold vivo seven 11 Japanese. 1.6 4.9. significantly triazolam. Only partial success predicting ethnic indicates need larger more reliable databases variables. With such information, silico might be used confidence decrease repeating pharmacokinetic studies groups.