Abstract
The absorption, distribution, excretion, and metabolic fate of cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl)-benzylidenyl]-indene-3-acetic acid (I) were investigated in the dog, rat, rhesus monkey, and man. The drug was well absorbed after oral administration in all species and was excreted primarily in feces of dogs and rats, but in urine of monkeys and humans. I and/or its metabolites were widely distributed in rat tissues, with levels in plasma being higher than those in tissues. Rat plasma levels were much higher than those in other species after administration of equal doses. I was highly bound in plasma of all species. Biliary excretion was extensive in the dog and rat. Unchanged drug and two metabolites, the sulfone (II) and sulfide (III) analogs, were identified in plasma, urine, bile, and feces of the various species. III was pharmacologically active as an anti-inflammatory agent. I and II, both free and as glucuronide conjugates, were the principal metabolites in human urine. III was not found in human urine. A polar metabolite, IV, tentatively identified as cis-5-fluoro-2-hydroxymethyl-1-[p-(methylsulfinyl)-α-hydroxybenzyl]indene-3-acetic acid, was also isolated from human urine.
Footnotes
- Received June 8, 1973.
- Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics
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