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Impact of genetic polymorphisms of cytochrome P450 2 C (CYP2C) enzymes on the drug metabolism and design of antidiabetics
Authors:Sun Hao  Scott Dennis O
Affiliation:Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Groton, CT, United States. hao.sun@pfizer.com
Abstract:CYP2C enzymes are responsible for the oxidative metabolism of a diverse number of drugs for the treatment of type 2 diabetes mellitus, a severe metabolic disorder with high prevalence. Various clinical studies found the close association between CYP2C polymorphisms and altered pharmacokinetics, toxicological profiles, and drug-drug interactions of antidiabetic drugs. In this brief review, we discussed the impact of CYP2C polymorphisms on the metabolic fate of small-molecule antidiabetics including sulfonylureas, meglitinides, thiazolidinediones, gliptins, and gliflozins, with the key drug-protein molecular interactions highlighted.
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