Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam.

The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg x 5. Cimetidine significantly impaired (p = 0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7 +/- 21.9 h to 72.6 +/- 39.4 h (mean +/- SD), and a decrease in total plasma clearance from 12.0 +/- 2.7 ml/min to 8.6 +/- 3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.