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Drinking Ethanol Has Few Acute Effects on CYP2C9, CYP2C19, NAT2, and P‐Glycoprotein Activities but Somewhat Inhibits CYP1A2, CYP2D6, and Intestinal CYP3A: So What?
Author(s) -
Gazzaz Malaz,
Kinzig Martina,
Schaeffeler Elke,
Jübner Martin,
Hsin Chihhsuan,
Li Xia,
Taubert Max,
Trueck Christina,
IltgenBreburda Juliane,
Kraus Daria,
Queckenberg Christian,
Stoffel Marc,
Schwab Matthias,
Sörgel Fritz,
Fuhr Uwe
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1083
Subject(s) - dextromethorphan , pharmacology , paraxanthine , cyp2c19 , crossover study , tolbutamide , cyp2d6 , cyp2c9 , chemistry , cyp1a2 , cyp3a , caffeine , pharmacokinetics , p glycoprotein , dextrorphan , midazolam , omeprazole , endocrinology , medicine , enzyme , biochemistry , cytochrome p450 , alternative medicine , pathology , multiple drug resistance , sedation , placebo , antibiotics , diabetes mellitus
We quantified the effect of acute ethanol exposure (initial blood concentrations 0.7 g/L) on major drug metabolizing enzymes and p‐glycoprotein. Sixteen healthy Caucasians participated in a randomized crossover study with repeated administration of either vodka or water. Enzyme/transporter activity was assessed by a cocktail of probe substrates, including caffeine (CYP1A2/NAT2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P‐glycoprotein). The ratio of AUC 0‐t of dextromethorphan for ethanol/water coadministration was 1.95 (90% confidence interval (CI) 1.48–2.58). The effect was strongest in individuals with a CYP2D6 genotype predicting high activity ( n = 7, ratio 2.66, 90% CI 1.65–4.27). Ethanol increased caffeine AUC 0‐t 1.38‐fold (90% CI 1.25–1.52) and reduced intestinal midazolam extraction 0.77‐fold (90% CI 0.69–0.86). The other probe drugs were not affected by ethanol. The results suggest that acute ethanol intake typically has no clinically important effect on the enzymes/transporters tested.