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 (mean +/- SD). During concomitant treatment with diazepam and cimetidine these concentrations rose to 194 +/- 52 ng/ml and 255 +/- 46 ng/ml (P less than 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.

RCT Entities:   Population Interventions Outcomes