Metabolism of aspirin and procaine in mice pretreated with O-4-nitrophenyl methyl(phenyl)phosphinate or O-4-nitrophenyl diphenylphosphinate.
Concentrations of [carboxyl-14C]procaine in blood of mice were increased threefold for 27 min by exposure to O-4-nitrophenyl diphenylphosphinate 2 hr prior to [carboxyl-14C]procaine injection ip, while there was no effect of O-4-nitrophenyl methyl(phenyl)phosphinate pretreatment. There was no effect of either organophosphinate on the primary hydrolysis of [acetyl-l-14C]aspirin when assessed by the expiration of [14C]carbon dioxide; however, O-4-nitrophenyl diphenylphosphinate pretreatment produced transient increases in blood concentrations of both [carboxyl-14C]aspirin and [carboxyl-14C]salicylic acid following administration of [carboxyl-14C]aspirin. Liver carboxylesterase activity in O-4-nitrophenyl diphenylphosphinate pretreated mice was 11% of control activity. These results indicate the potential for drug interaction with O-4-nitrophenyl diphenylphosphinate but not with O-4-nitrophenyl methyl(phenyl)phosphinate. It appears that liver carboxylesterase activity has a minor role in hydrolysis of aspirin in vivo, but may be more important in procaine metabolism.
D000818:Animals; D001241:Aspirin / Q000097:blood / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006868:Hydrolysis; D007273:Injections, Intramuscular; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009578:Nitrobenzenes / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D011343:Procaine / Q000097:blood / Q000378:metabolism*; D012737:Sex Factors
D002250:Carbon Radioisotopes; D009578:Nitrobenzenes; D009943:Organophosphorus Compounds; C049497:O-4-(nitrophenyl)diphenyl phosphinate; C049498:O-4-(nitrophenyl)methylphenyl phosphinate; D011343:Procaine; D002265:Carboxylic Ester Hydrolases; D001241:Aspirin