Metabolism of the (+)-, (+/-)-, and (-)-enantiomers of alpha-methylfluorene-2-acetic acid (cicloprofen) in rats

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
A V DeanE C Schreiber

Abstract

1. After oral or intraperitoneal administration of (+/-)-[14C]cicloprofen to rats, the peak plasma concentrations of radioactivity and the areas under the plasma concentration/time curves did not increase proportionally with dose; total urinary and faecal excretions of radioactivity did increase with dose, suggesting saturation of plasma protein binding of drug and faster elimination of unbound drug at higher doses. 2. [14C]Cicloprofen and its metabolites were eliminated mainly via biliary excretion. Ratios of faecal to urinary excretion ranged from 2 to 3 and depended on dose administered. 3. Rats with cannulated bile ducts excreted the drug almost exclusively in bile, whereas intact rats excreted up to 32% of the dose in urine in 6 days, suggesting that [14C]cicloprofen or its metabolites or both undergo extensive enterohepatic recirculation in the rats. 4. The major metabolites of [14C]cicloprofen excreted in urine or bile were the 7-hydroxy, 9-hydroxy-, 7,9-dihydroxy-, and 9-hydroxy-9-methoxy-derivatives and their glucuronide or sulphate conjugates. 5. The (+)-enantiomer of [14C]cicloprofen was hydroxylated and excreted by rats at a faster rate than its (-)-antipode; no qualitative stereoselective metabolism of the individu...Continue Reading

References

Feb 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S J LanA I Cohen
Jul 1, 1979·Journal of Pharmaceutical Sciences·T IshidaT Aratani
Nov 1, 1981·Journal of Pharmaceutical Sciences·J K StoltenborgF M Vane
Nov 1, 1992·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·T Ishida, T Matsumoto

Citations

Mar 1, 1976·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K J KripalaniE C Schreiber
Jan 1, 1973·Drug Metabolism Reviews·P Jenner, B Testa
Oct 1, 1972·Journal of Medicinal Chemistry·E T StillerS D Levine

Related Concepts

Metabolic Process, Cellular
Derivatives
Structure-Activity Relationship
Anti-Inflammatory Agents
Fluorenes
Body Excretions
Metabolic Pathway
Excretory Function
Bile Duct Structure
Enantiomer

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