In:
Drug Metabolism and Personalized Therapy, Walter de Gruyter GmbH, Vol. 37, No. 1 ( 2022-04-05), p. 55-67
Abstract:
Khat, a natural amphetamine-like psychostimulant plant, are widely consumed globally. Concurrent intake of khat and xenobiotics may lead to herb-drug interactions and adverse drug reactions (ADRs). This study is a continuation of our previous study, targeted to evaluate the in vitro inhibitory effects of khat ethanol extract (KEE) on human cytochrome (CYP) 1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, and CYP3A5, major human drug metabolizing enzymes. Methods In vitro fluorescence enzyme assays were employed to assess CYPs inhibition with the presence and absence of various KEE concentrations. Results KEE reversibly inhibited CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2 and CYP3A5 but not CYP1A2 with IC 50 values of 25.5, 99, 4.5, 21, 27, 17, and 10 μg/mL respectively. No irreversible inhibition of KEE on all the eight CYPs were identified. The K i values of CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2 and CYP3A5 were 20.9, 85, 4.8, 18.3, 59.3, 3, and 21.7 μg/mL, respectively. KEE inhibited CYP2B6 via competitive or mixed inhibition; CYP2E1 via un-competitive or mixed inhibition; while CYP2A6, CYP2C8, CYP2C19, CYP2J2 and CYP3A5 via non-competitive or mixed inhibition. Conclusions Caution should be taken by khat users who are on medications metabolized by CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, and CYP3A5.
Type of Medium:
Online Resource
ISSN:
2363-8915
DOI:
10.1515/dmpt-2021-1000196
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2022
detail.hit.zdb_id:
2822040-7
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