Elevation of steady-state diazepam levels by cimetidine

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Abstract
The effect of cimetidine (1000 mg/day) on steady-state diazepam (5 mg/day) kinetics was investigated in 6 healthy subjects. During placebo-controlled treatment for 11 days, trough steady-state plasma levels were 130 .+-. 33 ng/ml and stready-state concentration averaged 185 .+-. 57 ng/ml (.hivin.x [mean] .+-. SD). During concomitant treatment with diazepam and cimetidine these concentrations rose to 194 .+-. 52 and 255 .+-. 46 ng/ml (P < 0.002). The 40-50% increase was due to reduction (P = 0.026) of total body clearance from 20.9 .+-. 9.5 (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 to 101 .+-. 58.1 h) by cimetidine.

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