COMPARATIVE METABOLISM OF FENCLORAC IN RAT, DOG, MONKEY, AND MAN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (2) , 122-131
Abstract
Fenclorac (.alpha.-m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, [rhesus] monkey and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during the absorption and elimination phases in all species. Small quantitites of m-chloro-p-cyclohexylphenylglycolic acid metabolite were present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 h in the rat to 6.5 h in the dog. The principle tissues of distribution were liver, kidney and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant[Mycobacterium butyricum]-induced polyarthritis.