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Isolation And Pharmacological Characterization Of Microsomal Human Liver Flumazenil Carboxylesterase

By Britta Kleingeist, Ronald Böcker, Gerd Geisslinger and Department Of Experimental

Abstract

ABSTRACT. Purpose. In vivo the biotransformation of the imidazobenzodiazepine antagonist flumazenil leads to the formation of two metabolites, flumazenil acid and N-demethylated flumazenil. In the present study we investigated the role of carboxylesterases for the metabolism of flumazenil. Methods. We purified a non-specific carboxylesterase (EC 3.1.1.1) from human liver microsomes that catalyzes the hydrolysis of flumazenil to flumazenil acid and, in presence of methanol the formation of flumazenil methylester an in vivo unknown metabolite. The purification procedure included solubilization of the microsomes obtained from human livers with Triton X-100 and subsequent chromatography of the 100000 x g supernatant on blue-sepharose, DEAE-sepharose, hydroxyapatite an

Year: 2013
OAI identifier: oai:CiteSeerX.psu:10.1.1.320.768
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