Contributions of UDP-Glucuronosyltransferases to Human Hepatic and Intestinal Metabolism of Ticagrelor and Inhibition of UGTs and Cytochrome P450 Enzymes by Ticagrelor and its Glucuronidated Metabolite.

ABSTRACT: Ticagrelor is the first reversibly binding, direct-acting, oral P2Y₁₂ receptor inhibitor. The contribution of UDP-glucuronosyltransferases (UGTs) enzymes to the metabolism of ticagrelor to its glucuronide conjugation, ticagrelor-O-glucuronide, in human liver microsomes (HLM) and human intestinal microsomes (HIM), was well characterized in the current study. The inhibition potential of human major UGTs by ticagrelor and ticagrelor-O-glucuronide was explored. The inhibitory effects of ticagrelor-O-glucuronide on cytochrome P450s (CYPs) enzymes were investigated as well. Ticagrelor glucuronidation exhibits substrate inhibition kinetics in both HLM and HIM with apparent K_m values of 5.65 and 2.52 μM, V_max values of 8.03 and 0.90 pmol min^-1·mg protein

SUBMITTER: Liu S 

PROVIDER: S-EPMC8552062 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature