An investigation of the metabolic activity, isozyme contribution, species differences and potential drug-drug interactions of PI-103, and the identification of efflux transporters for PI-103-O-glucuronide in HeLa1A9 cells.

ABSTRACT: PI-103 is a phosphatidylinositol 3-kinase inhibitor that includes multiple receptor affinity modifications, and it is also a therapeutic drug candidate primarily for human malignant tumors. However, its metabolic fate and potential drug-drug interactions involving human cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) enzymes remain unknown. In this study, our results demonstrated that the intrinsic clearance (CL_int) values of oxidated metabolite (M1) in human liver microsomes (HLM) and human intestine microsomes (HIM) were 3.10 and 0.08 μL min^-1 mg^-1, respectively, while PI-103 underwent efficient glucuronidation with CL_int values of 15.59 and 211.04 μL min^-1 mg^-1 for mono-glucuronide (M2) by HLM and HIM, respec

SUBMITTER: Gao L 

PROVIDER: S-EPMC9050161 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature