Prediction of hepatic and intestinal glucuronidation using in vitro-in vivo extrapolation.

摘要: The accurate prediction of hepatic (Fh) and intestinal availability (Fg) is vital for determining human pharmacokinetics. To predict these PK parameters cytochrome P450 (P450) metabolism, in vitro-in vivo extrapolation (IVIVE) using microsomes, hepatocytes, microsomes has been actively investigated. However, IVIVE not sufficiently evaluated non-P450 enzymes. UDP-glucuronosyltransferase (UGT) a enzyme that catalyzes glucuronidation, major pathway drugs possessing carboxylic acid, hydroxyl, amine moieties. In drug UGT the most important after P450, Fh substrates mainly attempted models based on clearance concepts. While various approaches achieving improved have investigated--such as addition bovine serum albumin to microsomal incubation mixtures--optimized vitro methods utilize both hepatocytes more are still required. Although application simplified (SIA) model effective predicting Fg substrates, this limited compounds with high oral absorption. review, we discuss current state, issues, future directions glucuronidation.