Inhibitory effect of typical CYP inhibitors under long term incubation in human liver microsomes

Inhibitory effect of typical CYP inhibitors under long term incubation in human liver microsomes

Published:  10/5/2018 1:39:14 PM

Presented at the 33rd JSSX Annual Meeting / 2018 MDO Meeting in Japan
Sho Nishinoaki, Ryo Fujino, Kenta Hashizume, Tsutomu Negama
Drug Development Solutions Center, Drug Development Solutions Division, Sekisui Medical Co., Ltd. 2117 Muramatsu, Tokai, Ibaraki 319-1182, Japan

Cytochrome P450 (CYP) isoforms are responsible for the metabolism of the majority of drugs in human. In case of the metabolic enzyme identification of CYP isoforms for the low intrinsic clearance (CLint) candidate compounds, it is necessary to perform metabolic reaction with long term incubation. In addition, when performing the metabolic enzyme identification with long term incubation, the specificity and sustainability of a typical inhibitor are important. In this research, we evaluated the inhibitory effect of typical inhibitor for each CYP isoform in human liver microsomes (HLM) under long term incubation (incubation time of CYP typical inhibitors was 60 minutes, final concentration of HLM was 1 mg protein/mL) to clarify an optimal concentration of the CYP typical inhibitors under long term incubation. In this presentation, we have confirmed specificity and sustainability of each typical inhibitor for CYP isoform under long term incubation in HLM.

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