Nocturnal Doses of Ranitidine and Nizatidine Do not Affect the Disposition of Diazepam

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Abstract
The disposition of diazepam (D) after a single oral dose of 10 mg was evaluated in nine healthy male volunteers under the following conditions (randomized, double‐blind, crossover design): D + comedication of placebo and D + nocturnal dosing with 300 mg ranitidine or 300 mg nizatidine. Plasma concentrations of D and its major active metabolite, desmethyldiazepam (DD), were monitored by a gas‐liquid chromatography‐electron‐capture detection assay for 84 hours. Neither ranitidine nor nizatidine had any significant effect on the hepatic elimination of D as characterized by its terminal half‐life (mean ± SD) of 35.3 ± 24.2 hours (+ ranitidine: 30.1 ± 9.9 hr; + nizatidine: 37.3 ± 18.3 hr) or total plasma clearance of 28.2 ± 12.0 mh/min (+ ranitidine: 26.5 ± 7.9 mL/min; + nizatidine: 26.7 ± 10.4 mL/min). Likewise, the formation of DD as measured by its AUC was not affected by ranitidine or nizatidine. Thus, it can be concluded that concomitant once‐daily dosing (300 mg nocturnally) with ranitidine or nizatidine does not impair hepatic drug metabolism.