Premium
Interaction of Diazepam With Famotidine and Cimetidine, Two H 2 ‐Receptor Antagonists
Author(s) -
Locniskar Ann,
Greenblatt David J.,
Harmatz Jerold S.,
Zinny Michael A.,
Shader Richard I.
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb03527.x
Subject(s) - famotidine , diazepam , cimetidine , volume of distribution , chemistry , pharmacology , pharmacokinetics , histamine h2 receptor , drug interaction , antagonist , medicine , receptor , biochemistry
Famotidine is currently under investigation as an H 2 ‐receptor antagonist. Eleven healthy male volunteers received a single 10 mg intravenous dose of diazepam on three occasions: once during coadministration of famotidine 40 mg bid, once during coadministration of cimetidine 300 mg qid, and once without other drug treatment (control). Multiple blood samples were drawn during the seven days after each diazepam dose. Diazepam and desmethyldiazepam plasma concentrations were measured by electron capture gas chromatography. There were no significant differences among the three treatment conditions in diazepam central compartment volume or total volume of distribution. During the cimetidine as compared with the control treatment, diazepam elimination half‐life was significantly increased (72 vs 55 hr , P < .05), total area under the curve (AUC) increased (11.8 vs 9.8 hr‐μg/mL , P < .05), and total clearance reduced (0.20 vs 0.28 mL/min/kg , P < .05). Seven‐day AUC for desmethyldiazepam also increased (4.6 vs 3.8 hr‐μg/mL , P < .05). However, there were no significant differences between famotidine and control treatment conditions in diazepam elimination half‐life (53 vs 55 hr), total AUC (9.5 vs 9.8 hr‐μg/mL), or total clearance (0.28 vs 0.28 mL/min/kg) or in seven‐day AUC for desmethyldiazepam (3.9 vs 3.8 hr‐μg/mL). Thus, therapeutic doses of cimetidine significantly impair the clearance of diazepam and desmethyldiazepam. Therapeutic doses of famotidine do not impair diazepam and desmethyldiazepam kinetics, suggesting that there is no significant kinetic interaction when diazepam and famotidine are administered concurrently in clinical practice .