Dataset Information

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

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?

SUBMITTER: Bedada W

PROVIDER: S-EPMC6109098 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Bedada Worku W de Andrés Fernando F Engidawork Ephrem E Hussein Jemal J LLerena Adrián A Aklillu Eleni E

Scientific reports 20180824 1

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 wer ...[more]

PMID: 30143732

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Project description:BackgroundKhat is amphetamine-like substance commonly consumed by students when they wish to study for long hours especially during examination periods. Khat consumption is associated with increased rates of cardiovascular problems, stroke, myocardial infarction, cardiomyopathy, periodontal disease, gastritis, poor oral hygiene, psychosis, decreased quality of life, and poor academic performance.MethodsPubMed, EMBASE, and SCOPUS were systematically searched without restriction by publication status. Publications were screened according to predefined inclusion criteria. Twenty-five articles were included. Random effect model was used to calculate weighted prevalence, odds ratio (OR) and corresponding 95% confidence interval (CI). We assessed the risk of publication bias by using funnel plot and Eggers's regression tests.ResultsThe pooled prevalence of current khat use among university students was 14.16% (95% CI; 11.87-16.81). The pooled prevalence of current khat use was highest in Saudi Arabia 18.85% and it was 13.59% in Ethiopia and 13.04% in Yemen. In addition, the current pooled prevalence of khat use was higher in men at 19.26% than in women 6.41%. Regarding lifetime khat use, in this study, the pooled prevalence of lifetime khat use was 27.31%. The lifetime prevalence was higher in men at 31.47% than in women 11.79%. Moreover, the lifetime prevalence of khat use was 43.27% in Yemen, 37.32% in Saudi Arabia, and 24.82% in Ethiopia. We found significantly increased odds of current (OR 3.59; 95%CI 2.01-6.41) as well as lifetime (OR 3.48; 95%CI 2.09-5.78) khat chewing in men as compared to women.ConclusionThe pooled prevalence of current and lifetime khat consumption was 14.16 and 27.31%, respectively. Both the current and lifetime prevalence of khat use was higher in men than in women. In addition, both the current and lifetime prevalence estimates of khat consumption were low in Ethiopia than in Saudi Arabia. Moreover, the odds of both current and lifetime khat consumption were higher in male students than in female students. Programmes that specifically aim at increasing awareness and that most motivate reduced khat consumption among university students were recommended.

Dataset Information

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

Publications

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

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