Elevation of steady‐state diazepam levels by cimetidine

The effect of cimetidine (1000 mg/day) on steady‐state diazepam (5 mg/day) kinetics was investigated in six healthy subjects. During placebo‐controlled treatment for 11 days, trough steady‐state plasma levels were 130 ± 33 ng/ml and steady‐state concentration averaged 185 ±57 ng/ml (x̄ ± SD). During concomitant treatment with diazepam and cimetidine these concentrations rose to 194 ± 52 ng/ml and 255 ± 46 ng/ml (P < 0.002). The 40% to 50% increase was due to reduction (P = 0.026) of total body clearance from 20.9 ± 9.5 ml/min (control) to 14.0 ± 3.0 ml/min (with cimetidine). Diazepam elimination half‐life was also prolonged (P = 0.02, from 39.5 ± 16.6 hr to 101 ± 58.1 hr) by cimetidine. Clinical Pharmacology and Therapeutics (1981) 30, 513–517; doi: 10.1038/clpt.1981.196