Nocturnal doses of ranitidine and nizatidine do not affect the disposition of diazepam.
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 mL/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.
D000328:Adult; D003975:Diazepam / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016567:Nizatidine; D003708:Nordazepam / Q000097:blood; D011899:Ranitidine / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D013844:Thiazoles; D003708:Nordazepam; D011899:Ranitidine; D016567:Nizatidine; D003975:Diazepam