Nov 1, 1975

Physiological disposition and metabolism of 5-(2',4'-difluorophenyl)salicyclic acid, a new salicylate

Drug Metabolism and Disposition : the Biological Fate of Chemicals
D J ToccoC V Perrier

Abstract

5-(2'4'-Difluorophenyl) [carboxy-14C]salicyclic acid (MK-647) was quickly and completely absorbed in rats, dogs, and man. Peak levels of plasma radioactivity occurred in 1-2 hr after oral administration. The dose was 10 mg/kg in rats and dogs, and 50 or 500 mg in man. Most of the drug in plasma was intact MK-647 which was extensively bound to plasma protein. In man the peak concentration following the 500-mg dose was approximately 10 times that after the lower dose, which suggests that absorption rates of both doses were similar. Elimination of drug from plasma was dose-dependent. The area under the curve for MK-647-14C in plasma was 18 times higher following the 500-mg dose than the 50-mg dose. Dogs given 10 mg/kg orally or intravenously excreted 44% of the dose in the urine and 42% in the feces in 72 hr. Rats given the same dose level by either route of administration excreted 80% in the urine and 11% in the feces. In man approximately 95% of a 50- or 500-mg oral dose was excreted in the urine and 3% in the feces, in 96 hr. MK-647 and two metabolites were present in the urine of three species. The ether and ester glucuronides were identified in human urine. The latter metabolite was also identified in rat and dog urine. The g...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
Urine
Human urine
Prothrombin Time Assay
Ethers
Serum Proteins
Etherum, ether, Homeopathic preparation
Plasma Protein Assay
Salicylates
Glucose Tolerance Test

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