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Reinterpretation of the Pharmacokinetic Mechanism of Oral Benzodiazepine Ethanol Interaction
Author(s) -
Guthrie Sally K.,
Lane Elizabeth A.
Publication year - 1986
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1986.tb05169.x
Subject(s) - benzodiazepine , pharmacokinetics , chemistry , cmax , ethanol , pharmacology , oral administration , elimination rate constant , absorption (acoustics) , biochemistry , volume of distribution , medicine , materials science , receptor , composite material
Previously published studies investigating the oral benzodiazepine ethanol interaction have utilized a single dose of ethanol, a single dose of oral benzodiazepine, and measured plasma benzodiazepine concentration over varying time periods. Most studies reported an increase or no change in benzodiazepine plasma concentrations following ethanol administation, which the investigators usually ascribed to an ethanoi‐induced increase in the benzodiazepine absorption rate constant However, ethanol decreases the hepatic clearance of benzodiazepines that are biotransformed via the P450 enzyme system and this effect was not taken into account in evaluation of the results of these studies. Computer simulations have been used to investigate possible mechanisms of the oral benzodiazepine‐ethanol interaction. The effects of a constant or transient decrease in clearance and an increase or decrease in absorption rate constant upon maximum concentration, time of maximum concentration, and area under the benzodiazepine plasma concentration curve (AUC) have been examined. A transient 75% decrease in benzodiazepine clearance resulted in a 13.6% increase in AUC (0–36 hr), a 3.4% increase in C max and a 5.7% increase in t max These changes are qualitatively consistent with, but quantitatively shy, of those observed in most studies. Consequently, an effect of ethanol upon benzodiazepine absorption must still be considered.