Abstract
Cimetidine has been shown to inhibit the liver microsomal metabolism of the benzodiazepines diazepam and chlordiazepoxide, resulting in an increase in half-life and decrease in the clearance of these two drugs. Patients receiving the combination of diazepam and cimetidine have been noted to be more sedated than when given an equal dose of diazepam alone. Many benzodiazepines undergo N-dealkylation and hydroxylation via the cytochrome P450 oxidase system. Cimetidine is thought to bind to cytochrome P450 oxidase and to interfere with many drugs using this path way. Oxazepam and lorazepam are two benzodiazepines not oxidatively metabolized by cytochrome P450, but are glucuronidated by glucuronyl transferase and are, therefore, not subject to metabolic inhibition by cimetidine. Thus, when clinically indicated, oxazepam and lorazepam may be the benzodiazepines of choice to use in combination with cimetidine to eliminate the clinically significant drug interaction seen with diazepam and chlordiazepoxide.
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