The effect of cimetidine on the pharmacodynamics of theophylline-induced seizures and ethanol hypnotic activity.
Due to its availability as an over-the-counter drug, the use of cimetidine is increasing, thus adverse interactions with other commonly used agents may also increase. The aim of this study was to investigate whether acute administration of cimetidine could alter the pharmacodynamics of theophylline neurotoxicity and the hypnotic action of ethanol. To examine these questions, rats received a dose of 77 mg/kg cimetidine followed by a constant infusion of either theophylline (1.2 mg/min.) or ethanol (16.3 mg/min.) until the onset of the pharmacological end point, maximal seizure or loss of righting reflex, where samples of blood and brain were obtained and assayed for either theophylline or ethanol. We report that cimetidine in doses that may cause pharmacokinetic interactions did not affect the concentration-effect relationship of either the stimulating action of theophylline or the depressant activity of ethanol. These outcomes emphasize the relative safety which patients using cimetidine in self-medication rely on.
Hoffman
A
A
Department of Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, Israel. ahoffman@cc.huji.ac.il
Perlstein
I
I
Habib
G
G
Pinto
E
E
Gilhar
D
D
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006990:Hypnosis; D011187:Posture / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012021:Reflex, Abnormal / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013806:Theophylline / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D000431:Ethanol; D002927:Cimetidine; D013806:Theophylline