Effect of short-term ethanol administration on lorazepam clearance.

Abstract

The disposition of chlordiazepoxide (Librium) and diazepam (Valium), compounds which are initially degraded by oxidative processes, differs from that of oxazepam (Serax) and lorazepam (Ativan, drugs which are inactivated by conjugation with glucuronic acid. Liver disease and cimetidine impair the elimination of the former agents, but not the latter two benzodiazepines. In addition, ethanol inhibits the metabolism of chlordiazepoxide and diazepam. The present studies were performed to determine the effect of short-term ethanol administration on glucuronidation and elimination of lorazepam in dogs and humans. Because, in dogs, lorazepam has a high extraction ratio (approximately 0.9) with an a..