Ethanol inhibits in-vitro metabolism of nifedipine, triazolam and testosterone in human liver microsomes.

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Citation

Patki KC, Greenblatt DJ, von Moltke LL

Ethanol inhibits in-vitro metabolism of nifedipine, triazolam and testosterone in human liver microsomes.

J Pharm Pharmacol. 2004 Aug;56(8):963-6. doi: 10.1211/0022357043950.

PubMed ID
15285839 [ View in PubMed
]
Abstract

Although extended exposure to ethanol induces CYP3A metabolism in-vivo, the acute effects of ethanol on CYP3A metabolism have not been fully evaluated in-vitro. We assessed the effect of ethanol on CYP3A-mediated biotransformation using human liver microsomes in-vitro with three prototypic CYP3A-mediated reactions: nifedipine to oxidized nifedipine, triazolam to its 1-hydroxy (1-OH TRZ) and 4-hydroxy (4-OH TRZ) metabolites, and testosterone to 6beta-hydroxytestosterone (6beta-OH TST). Ethanol inhibited metabolism of nifedipine (oxidized nifedipine IC50 3 mg dL(-1), where the IC50 value is the inhibitor concentration corresponding to a 50% reduction in metabolite formation velocity), triazolam (1-OH TRZ IC50 1.1 mg dL(-1), 4-OH TRZ IC50 2.7 mg dL(-1)) and testosterone (6beta-OH TST IC50 2.4 mg dL(-1)). The inhibitory potency of ethanol was similar for the three substrates representing the three hypothetical CYP3A substrate categories. The IC50 values obtained were lower than clinically relevant blood alcohol concentrations. In conclusion, ethanol is an inhibitor of human CYP3A metabolism and may contribute to clinically important interactions.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
EthanolCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Drug Interactions
DrugsInteraction