Cimetidine impairs nitrazepam clearance

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Abstract
The effect of cimetidine [an antiulcer drug] on hepatic clearance of the benzodiazepine derivative nitrazepam [a hypnotic] was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 h after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min per kg in the control state to 1.17 ml/min per kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t1/2 [half life] from 22.2 to 27.8 h. The ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.

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