DISPOSITION OF FLUNISOLIDE IN THE RAT, MOUSE, DOG, RHESUS-MONKEY, AND CYNOMOLGUS MONKEY

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (2) , 81-89
Abstract
Flunisolide (6.alpha.-fluoro-11.beta.,16.alpha.,17.alpha.,21-tetrahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide) administered as a single i.v. or oral dose to rats, mice, dogs, rhesus monkeys and cynomolgus monkeys had a plasma t1/2 [half-life] of 1-3.5 h and was eliminated mainly via the bile. After i.v. administration of 14C-labeled flunisolide, radioactivity was widely distributed into tissues and organs. The apparent volume of distribution of flunisolide in these 5 spp. was 3.0-8.0 l/kg. A major metabolite isolated from rhesus monkey urine was 6.beta.,11.beta.,16.alpha.,17.alpha.,21-pentahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide (6.beta.-OH metabolite). Free 6.beta.-OH metabolite was a major radioactive entity detected in urine of all species given radiolabeled flunisolide, whereas flunisolide conjugated with glucuronic acid and/or sulfate was a major metabolite detected in the bile of rats, dogs and cynomolgus monkeys. Following the oral administration of radiolabeled flunisolide, radioactivity was rapidly and efficiently absorbed in all species, but in the rhesus and cynomolgus monkeys most of the plasma radioactivity was due to the 6.beta.-OH metabolite and to water-soluble conjugates, suggesting extensive 1st-pass metabolism of flunisolide. Flunisolide is a potent corticoid.

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