Drug-drug interaction of atazanavir on UGT1A1-mediated glucuronidation of molidustat in human.

ABSTRACT: Molidustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl-hydroxylase enhancing the erythropoietin (EPO) response to HIF; it is in clinical development for the treatment of anaemia related to chronic kidney disease. The predominant role of glucuronidation for molidustat clearance (formation of N-glucuronide metabolite M1) and subsequent renal excretion was confirmed in a human mass balance study, with about 85% of the drug being excreted as M1 in urine. The inhibitory effects of 176 drugs and xenobiotics from various compound classes on the UGT-mediated glucuronidation of molidustat in human liver microsomes (HLMs) were investigated. Based on preclinical findings, glucuronidation of molidustat was predominantly mediated by the 5'-diphospho-glucuronosyltransferase (UGT) isofo

SUBMITTER: van der Mey D 

PROVIDER: S-EPMC7983974 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature