In vitro UGT assay for inhibition studies of benzodiazepines and opiates during phase II-metabolism

Hydroxy-benzodiazepines and opiates are metabolized through glucuronidation which is the predominant pathway in the clearance mechanism of exogenous and endogenous substances during phase II-metabolism. The reaction is catalyzed by uridine-diphosphoglucuronyltransferases (UGTs) [1]. The presented work is motivated by the fact that the combination of benzodiazepines and opiates is common both in clinical practice and as combined abuse. Inhibition of the glucuronidation can lead to a decelerated elimination of the phase I-metabolites, respectively of substances which are subjects of the phase II-metabolism. In the case of pharmacological and toxicological active substances, like the hydroxybenzodiazepines and opiates, this can result in a prolonged pharmacological activity and in a higher risk of side effects of these substances [2, 3]. Therefore an in vitro UGT-assay for inhibition studies between hydroxy-benzodiazepines and opiates has been developed and optimized using pooled human liver microsomes (HLMs).