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Research ArticleArticle

PHYSIOLOGICAL DISPOSITION OF FENOPROFEN IN MAN. III. METABOLISM AND PROTEIN BINDING OF FENOPROFEN

ALAN RUBIN, PATRICIA WARRICK, ROBERT L. WOLEN, STANLEY M. CHERNISH, ANTHONY S. RIDOLFO and CHARLES M. GRUBEIL JR.
Journal of Pharmacology and Experimental Therapeutics November 1972, 183 (2) 449-457;
ALAN RUBIN
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PATRICIA WARRICK
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ROBERT L. WOLEN
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STANLEY M. CHERNISH
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ANTHONY S. RIDOLFO
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CHARLES M. GRUBEIL JR.
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Abstract

We have conducted studies of the metabolism and protein binding of fenoprofen. dl-2-(3-phenoxyphenyl) propionic acid, in man. Urinary metabolites (as perecntage of administered dose) were: fenoprofen glucuronide (45%), 4'-hydroxyfenoprofen glucuronide (45%), 4'-hydroxyfenoprofen (2-5%) and unchanged fenoprofen (2-5%). Also excreted were an acid-labile conjugate of fenoprofen (2-5%), which does not appear to be a glycine or glutamine conjugate, and an acid-labile conjugate of 4'-hydroxyfenoprofen (2-5%), which does not appear to be a sulfate conjugate. Fenoprofen binding to protein was studied by dialysis and ultracentrifugation techniques. The compound was extensively and strongly bound to plasma albumin. Other drugs which are themselves protein bound were studied to learn whether they might displace fenoprofen from protein binding sites. When dialysis conditions were set to favor displacement, only phenylbutazone reduced fenoprofen binding; d-propoxyphene, indomethacin and aspirin had no such effect. In ultracentrifugation experiments, warfarin did not reduce fenoprofen binding over a wide range of warfarin concentrations; fenoprofen slightly reduced warfarin binding (94 to 91% bound) at fenoprofen concentrations considerably higer than expected for prolonged periods in vivo.

Footnotes

    • Received April 28, 1972.
    • Accepted June 30, 1972.
  • © 1972 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 183, Issue 2
1 Nov 1972
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Research ArticleArticle

PHYSIOLOGICAL DISPOSITION OF FENOPROFEN IN MAN. III. METABOLISM AND PROTEIN BINDING OF FENOPROFEN

ALAN RUBIN, PATRICIA WARRICK, ROBERT L. WOLEN, STANLEY M. CHERNISH, ANTHONY S. RIDOLFO and CHARLES M. GRUBEIL
Journal of Pharmacology and Experimental Therapeutics November 1, 1972, 183 (2) 449-457;

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Research ArticleArticle

PHYSIOLOGICAL DISPOSITION OF FENOPROFEN IN MAN. III. METABOLISM AND PROTEIN BINDING OF FENOPROFEN

ALAN RUBIN, PATRICIA WARRICK, ROBERT L. WOLEN, STANLEY M. CHERNISH, ANTHONY S. RIDOLFO and CHARLES M. GRUBEIL
Journal of Pharmacology and Experimental Therapeutics November 1, 1972, 183 (2) 449-457;
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