Metabolism of aspirin and procaine in mice pretreated with O-4-nitrophenyl methyl(phenyl)phosphinate or O-4-nitrophenyl diphenylphosphinate |
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| Authors: | J M Joly T M Brown |
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| Affiliation: | 1. Leading Technology of Bioanalysis and Protein Chemistry, SHIMADZU Corporation, Japan;2. SHIMADZU Bioscience Research Partnership, Shimadzu Scientific Instruments, United States;3. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Japan;4. Graduate School of Pharmaceutical Sciences, Kyoto University, Japan;1. Laboratory of Analytical, Bioanalytical Sciences and Miniaturization, UMR CBI 8231 ESPCI Paris, PSL University, Paris, France;2. Sorbonne Université, Paris, France;3. Laboratory of Physiopathology and PharmacoToxicology of the Human Placenta, UMR-S 1139 Inserm – University Paris Descartes, Sorbonne Paris Cité, Paris, France;1. Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR, United States;2. Toxicology Excellence for Risk Assessment, Cincinnati, OH, United States;3. Toxicology Consulting Services, Bonita Springs, FL, United States;4. Exponent, Midland, MI, United States |
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| Abstract: | 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. |
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