Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations

Scientific Reports
Worku BedadaEleni Aklillu

Abstract

In a one-way cross-over study, we investigated the effect of Khat, a natural amphetamine-like psychostimulant plant, on catalytic activities of five major drug-metabolizing cytochrome P450 (CYP) enzymes. After a one-week Khat abstinence, 63 Ethiopian male volunteers were phenotyped using cocktail probe drugs (caffeine, losartan, dextromethorphan, omeprazole). Phenotyping was repeated after a one-week daily use of 400 g fresh Khat leaves. Genotyping for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5 were done. Urinary cathinone and phenylpropanolamine, and plasma probe drugs and metabolites concentrations were quantified using LC-MS/MS. Effect of Khat on enzyme activities was evaluated by comparing caffeine/paraxanthine (CYP1A2), losartan/losartan carboxylic acid (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), dextromethorphan/dextrorphan (CYP2D6) and dextromethorphan/3-methoxymorphinan (CYP3A4) metabolic ratios (MR) before and after Khat use. Wilcoxon-matched-pair-test indicated a significant increase in median CYP2D6 MR (41%, p < 0.0001), and a marginal increase in CYP3A4 and CYP2C19 MR by Khat. Repeated measure ANOVA indicated the impact of CYP1A2 and CYP2C19 genotype on Khat-CYP enzyme interactions. The median MR increased by 3...Continue Reading

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Citations

Oct 28, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Kuntheavy Ing Lorenzini, François Girardin
May 6, 2021·Drug Metabolism and Personalized Therapy·Ibraheem M AttafiIbrahim A Khardali
Aug 20, 2021·Expert Opinion on Drug Metabolism & Toxicology·Eleni Aklillu, Ephrem Engidawork
Nov 26, 2021·Drug Metabolism and Personalized Therapy·Ibraheem M AttafiIbrahim A Khardali

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

Target [UNK]
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SPSS Statistics
GraphPad Prism
Quant Studio

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