Portal de Periódicos da CAPES

Pharmacokinetics of Salicylate Elimination in Man

1965; Elsevier BV; Volume: 54; Issue: 7 Linguagem: Inglês

10.1002/jps.2600540703

1520-6017

Gerhard Levy,

Pharmacogenetics and Drug Metabolism

Salicylate elimination kinetics was studied over a dose range of from 0.25 to 2.0 Gm. of aspirin. It was found that when the amount of salicylate in the body of normal adult test subjects exceeded approximately 360 mg. aspirin equivalent, conjugation of salicylic acid with glycine reached a maximum rate and thus proceeded by zero-order kinetics. The over-all elimination of salicylate was found to proceed by first-order kinetics at very small doses, and by parallel zero and first-order processes at higher doses. A kinetic model was developed, and values for appropriate rate constants were determined which make it possible to reconcile apparent half-lives for salicylate elimination ranging from about 3 hr. to over 20 hr. which have been reported in the literature. Unusual patterns in salicylate elimination kinetics observed by others, such as a change from zero to first-order kinetics upon concomitant administration of p-aminobenzoic acid, and zero-order elimination in a newborn infant, have been rationalized and interpreted by means of the kinetic model evolved from the present study. The pharmacokinetics of salicylate elimination were found to be unusual both qualitatively and quantitatively, and the results of the present study have potentially important therapeutic, toxicologic, and pharmacogenetic implications. Salicylate elimination kinetics was studied over a dose range of from 0.25 to 2.0 Gm. of aspirin. It was found that when the amount of salicylate in the body of normal adult test subjects exceeded approximately 360 mg. aspirin equivalent, conjugation of salicylic acid with glycine reached a maximum rate and thus proceeded by zero-order kinetics. The over-all elimination of salicylate was found to proceed by first-order kinetics at very small doses, and by parallel zero and first-order processes at higher doses. A kinetic model was developed, and values for appropriate rate constants were determined which make it possible to reconcile apparent half-lives for salicylate elimination ranging from about 3 hr. to over 20 hr. which have been reported in the literature. Unusual patterns in salicylate elimination kinetics observed by others, such as a change from zero to first-order kinetics upon concomitant administration of p-aminobenzoic acid, and zero-order elimination in a newborn infant, have been rationalized and interpreted by means of the kinetic model evolved from the present study. The pharmacokinetics of salicylate elimination were found to be unusual both qualitatively and quantitatively, and the results of the present study have potentially important therapeutic, toxicologic, and pharmacogenetic implications.