title: Carbaryl metabolism is inhibited by cimetidine in the isolated perfused rat liver and in man.
abstract: The potential for cimetidine to alter the metabolism of carbaryl has been investigated in the isolated perfused rat liver and in man. In the isolated perfused rat liver, carbaryl was removed by a high intrinsic clearance process, which was inhibited in a dose dependent fashion by cimetidine in the concentration range of 60-240 micrograms/ml. The pharmacokinetic profile in one subject for orally administered carbaryl was altered following administration of cimetidine (200 mg every eight hours for three days). The peak carbaryl level occurred 25 minutes later and was increased by twofold, due to a 46% reduction in apparent oral clearance. The observations indicate that cimetidine can inhibit the metabolism of carbaryl in both rat and man. These data suggest that administration of cimetidine to individuals exposed to carbaryl could result in enhanced toxicity.
mesh_terms: D000328:Adult; D000818:Animals; D012721:Carbaryl / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002927:Cimetidine; D006899:Mixed Function Oxygenases; D012721:Carbaryl