THE DISPOSITION AND METABOLISM OF 5-(4,5-DIHYDRO-2-PHENYLBENZ[E]INDOL-3-YL)SALICYLIC ACID (FENDOSAL) IN THE RAT, MOUSE, RABBIT, DOG, RHESUS-MONKEY, AND MAN

  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (2) , 161-167
Abstract
The disposition and metabolism of 5-(4,5-dihydro-2-phenylbenz[e]indol-3-yl)salicylic acid (fendosal) a new salicylate-type analgesic, was studied in the rat, mouse, rabbit, dog, rhesus monkey and man. Animals were given single oral or parenteral doses at levels of 5, 10 or 50 mg/kg; human volunteers received 200 mg orally. In all species, virtually all radioactivity was excreted in the feces. Biliary excretion accounted for approximately 50% of an oral dose in the rat and dog. Enterohepatic circulation was demonstrated in the rat. The compound was fairly rapidly absorbed in all species except the rhesus monkey. The principal excretion products found in all species were unchanged fendosal and a monohydroxylated metabolite, the latter being present both in the free state and as a glucuronide. A minor metabolite, present only in man and rhesus monkey, was tentatively identified as a dihydroxylated metabolite. These compounds were detected only in unpurified samples. During the isolation and purification procedure, oxidation occurred, resulting in the production of the corresponding dehydrogenated derivatives, which were the actual materials whose structures were elucidated.