Influence of cimetidine on the kinetics of diazepam and lorazepam.

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The influence of cimetidine on the kinetics of two benzodiazepines, diazepam and lorazepam, after a single oral dose (diazepam 5 mg or lorazepam 2 mg) was studied in 8 healthy male Japanese volunteers using an experimental design with two Latin squares. Cimetidine coadministration, 800 mg/day, was begun 24 hr prior to the benzodiazepine dose and continued during the trial. Cimetidine significantly prolonged the elimination half-life (P<0.05), increased the AUC (P <0.01), and decreased the clearance of diazepam (P <0.01), although it did not influence the peak plasma concentration, the time to reach peak concentration, and the volume of distribution of diazepam. However, cimetidine had a slight effect on the peak plasma concentration, the time to reach peak concentration, the elimination half-life, the AUC, the volume of distribution, and the clearance of lorazepam. The prolonged elimination half-life of diazepam with cimetidine coadministration was caused by decreased clearance of the drug. These results indicate that cimetidine influences differently the kinetics of diazepam and lorazepam due to the different metabolic characteristics of the two drugs, since lorazepam is directly biotransformed to glucuronide conjugates and diazepam is metabolized by reduction or oxidation prior to glucuronide conjugation.
一般社団法人日本臨床薬理学会の論文