Interaction of Cimetidine with Oxazepam, Lorazepam, and Flurazepam

Abstract: The influence of Cimetidine coadministration, 300 mg every 6 hours, on the kinetics of single oral doses of oxazepam (30 mg), lorazepam (2 mg), and flurazepam (30 mg) was evaluated in healthy volunteers. Cimetidine had no significant effect on the peak plasma concentration or the time of peak concentration for either oxazepam, lorazepam, or desalkylflurazepam (formed from flurazepam). Cimetidine likewise did not alter the elimination half‐life of oxazepam (9.4 hours) or lorazepam (11.6 hours), and did not change total AUC for lorazepam. Oxazepam AUC was increased an average of 10 per cent by Cimetidine (P < 0.02). In contrast, Cimetidine prolonged desalkylflurazepam elimination half‐life (141 vs. 94 hours, P < 0.1) and increased AUC an average of 65 per cent (P < 0.05). Thus, Cimetidine has little or no influence on the absorption or disposition of oxazepam and lorazepam, two benzodiazepines biotransformed by glucuronide conjugation. However, Cimetidine slows the elimination of flurazepam's metabolite, desalkylflurazepam, which is biotransformed by oxidation. 1984 American College of Clinical Pharmacology