Genetic polymorphisms of drug-metabolizing cytochrome P450 enzymes in cynomolgus and rhesus monkeys and common marmosets in preclinical studies for humans.

摘要: Cynomolgus monkeys (Macaca fascicularis, Old World Monkeys) and common marmosets (Callithrix jacchus, New have been widely, expectedly, used as non-human primate models in drug development studies. Major drug-metabolizing cytochrome P450 (P450) enzymes information is now available that supports these species animal models, it established multiple forms of cynomolgus monkey marmoset generally similar substrate recognition functionality to human enzymes. This research update provides on genetic polymorphisms like Information rhesus mulatta), another macaque metabolism studies, also included for comparison. Among a variety variants investigated, typical examples include individual pharmacokinetic data efavirenz R-warfarin associated with 2C9 (formerly 2C43) 2C19 (2C75) variants, respectively, R-omeprazole S-warfarin variants. These findings provide foundation understanding the toxicological results primates preclinical will help further support molecular mechanisms function. In addition polymorphic enzymes, effects aging some clearances mediated by were found elder animals or pretreated rifampicin. review describes acquired differences involved oxidation pharmacological and/or effects.