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Research ArticleArticle

METABOLISM AND BILIARY EXCRETION OF ETHACRYNIC ACID

Curtis D. Klaassen and Thomas J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics December 1974, 191 (3) 548-556;
Curtis D. Klaassen
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Thomas J. Fitzgerald
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Abstract

Within 4 hours after i.v. administration (5 or 50 mg/kg) of 14C-ethacrynic acid (EA), 60 to 70% was excreted into the bile of rats. Less than 25% was EA and the remainder was biotransformation products. The two major metabolites in bile were identified; one was the glutathione adduct of EA (EA-GSH) and the other was EA-mercapturate. Approximately 40% of either dose was excreted as EA-GSH. EA-mercapturate accounted for 18% of the low dose and 30% of the high dose excreted into bile. Dogs excreted 57% of a 5 mg/kg dose (i.v.) into bile within 4 hours. Less EA was metabolized by the dog than the rat; 38% of the radioactivity excreted into dog bile was in the form of the parent drug. In addition to the two metabolites of EA found in rat bile, the dog formed a cysteine adduct of EA (EA-cysteine). The dog excreted 25, 11 and 9% of the dose of EA as EA-mercapturate, EA-cysteine and EA-GSH, respectively. Seventeen percent of the 14C excreted into the bile remained unidentified.

Footnotes

    • Received May 6, 1974.
    • Accepted August 1, 1974.
  • © 1974 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 191, Issue 3
1 Dec 1974
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Research ArticleArticle

METABOLISM AND BILIARY EXCRETION OF ETHACRYNIC ACID

Curtis D. Klaassen and Thomas J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics December 1, 1974, 191 (3) 548-556;

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Research ArticleArticle

METABOLISM AND BILIARY EXCRETION OF ETHACRYNIC ACID

Curtis D. Klaassen and Thomas J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics December 1, 1974, 191 (3) 548-556;
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