Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes

Abstract

Abstract: AIM: To study the metabolic kinetics of CH330331 in rat liver microsome, and its inhibition on CYP450 subtypes in the “cocktail” models. METHODS: The incubation parameters in rat liver microsome were optimized and were the Michaelis-Menten parameters K_m and V_max estimated the component of probe inhibitors in “cocktail” models were also confirmed and the effect of CH330331 on main subtypes of cytochrome P450 studied. RESULTS: The K_m and V_max of CH330331 were 18.96 μmol/L and 2.08 μmol/(min·mg protein), respectively. CH330331 had a weakly inhibition to the activity of CYP1A2, CYP2D6 and CYP2C9 but had no effect on CYP2C19, CYP2E1, and CYP3A4. CONCLUSION: CH330331 can increase the blood concentration of those drugs that are metabolized mainly by CYP1A2, CYP2D6 and CYP2C9.

Key words: CH330331, Liver microsomes, CYP450, Cocktail

CLC Number:

R969

SUN Hai-yan, HE Fan, BI Hui-chang, HUANG Wen-lin, HUANG Min. Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(6): 607-612.

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