Noninteraction of temazepam and cimetidine

The possible kinetic interaction of the hypnotic temazepam and the H₂‐receptor antagonist cimetidine was evaluated. Nine healthy male and female volunteers received a 30‐mg oral dose of temazepam on two occasions in random sequence, separated by at least 1 week. On one occasion, temazepam was given in the otherwise drug‐free state; on the other, temazepam was given with concurrent administration of cimetidine, 300 mg every 6 h. Mean pharmacokinetic parameters for temazepam in control versus cimetidine trials were: peak plasma concentration, 560 versus 498 ng/mL; time of peak concentration, 2.0 versus 2.1 h after the dose; volume of distribution, 1.30 versus 1.39 L/kg; elimination half‐life, 9.9 versus 11.4 h; total clearance, 1.59 versus 1.60 mL/min/kg; free fraction of temazepam in plasma, 4.1 versus 3.8% unbound. Cimetidine has been shown to reduce the metabolic clearance of the benzodiazepines that are biotransformed by oxidative mechanisms. Temazepam, transformed by conjugation, appears unaffected by the coadministration of cimetidine.