Abstract
The metabolism of p-( cyclopropylcarbonyl) phenyl[14C]acetic acid (I-14C). a nonsteroidal anti-inflammatory agent. has been studied in rats. dogs. and monkeys. Animals were given single intravenous or oral doses of 5 and 50 mg of I-14C/ kg. In all cases. 72-88% of the administered dose was excreted in urine. with most of the radioactivity appearing within 24 hr after dosing; less than 1 1% was found in feces. The half-life (t½) of radioactivity in monkey or dog plasma was 1 and 5 hr. respectively. after the oral or intravenous administration of a 5-mg dose of I-14C per kg. At 50 mg/ kg. these half-lives increased to 3.5 and 7.7 hr. respectively. More than 90% of the radioactivity in plasma of both species was associated with unchanged drug. Species differences exist in the biotransformation of I. Rat urine contained 93-97% I; 2-6% ( a-cyclopropyl-a-hydroxy-p-tolyl) acetic acid ( II); and approximately 1% as conjugates. Monkey urine contained I-glucuronide ( 88%) and unconjugated II ( 7-10%). In the dog. l-taurine accounted for 27% of the radioactivity found in urine; II and its taurine conjugate accounted for 20 and 30%. respectively; a small quantity of li-glycine ( 3%) was also detected. There are three minor metabolites that have not been identified. Metabolite II isolated from dog urine was shown to be dextrorotatory.
Footnotes
- Received December 6, 1974.
- Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics
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