UGT InductionDrug Interactions
• Using HepaRG cell line or pooled human hepatocytes
• Using mRNA and/or UGT-activity level endpoints
A family of uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes is the most important group of enzymes involved in conjugative drug metabolism, catalysing addition of glucuronide acid to xenobiotics either directly or after oxidative (e.g. hydroxylation) metabolism. Interaction towards UGTs are under attention by regulatory authorities, especially in the cases where one of the major elimination pathways of the investigational drug is direct glucuronidation.
In addition to CYPs, also the UGT enzymes are inducible by new chemical entities. Of the inducible isoforms, UGT1A1 is the most relevant and abundant UGT enzyme. Induction assay is also available for UGT1A9 isoform. The assays deliver UGT induction relative to vehicle control (x-fold) and / or EC50 values if feasible (concentration where 50 % of maximal induction is achieved).