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Research ArticleArticle

PHARMACOKINETICS OF SALICYLAMIDE ELIMINATION IN MAN

Gerhard Levy and Tai Matsuzawa
Journal of Pharmacology and Experimental Therapeutics May 1967, 156 (2) 285-293;
Gerhard Levy
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Tai Matsuzawa
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Abstract

The pharmacokinetics of salicylamide elimination has been studied in healthy adult males and in two infants. Salicylamide is eliminated mainly by biotransformation to the glucuronide and the sulfate. The fraction of a dose which is excreted as salicylamide sulfate decreases with increasing dose, whereas the fraction excreted as glucuronide increases with increasing dose. The maximum excretion rate of salicylamide sulfate approaches a limiting value when 0.6 to 1.0 g of salicylamide is administered orally in rapidly absorbed form (solution) to adults. The limiting factor appears to be the availability of sulfate, since concomitant administration of L-cysteine increases the maximum excretion rate and the total excreted amount of salicylamide sulfate. Gentisamide glucuronide is a minor metabolite which appears in significant amounts only when salicylamide sulfate formation is restricted by the limited capacity of this process. Salicylamide in slowly absorbed form (pellets) yields larger amounts of salicylamide sulfate than the same dose in rapidly absorbed form (solution). These findings explain many of the apparent conflicts in previous reports on the metabolic fate of salicylamide in man, and they demonstrate that the metabolic fate of a drug which is eliminated by competing apparent zero-and first-order processes is a function of dose and dosage form, among other factors.

Footnotes

    • Received September 29, 1966.
    • Accepted November 9, 1966.
  • © 1967 by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 156, Issue 2
1 May 1967
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Research ArticleArticle

PHARMACOKINETICS OF SALICYLAMIDE ELIMINATION IN MAN

Gerhard Levy and Tai Matsuzawa
Journal of Pharmacology and Experimental Therapeutics May 1, 1967, 156 (2) 285-293;

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Research ArticleArticle

PHARMACOKINETICS OF SALICYLAMIDE ELIMINATION IN MAN

Gerhard Levy and Tai Matsuzawa
Journal of Pharmacology and Experimental Therapeutics May 1, 1967, 156 (2) 285-293;
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