BIOTRANSFORMATION OF THE STABLE PROSTACYCLIN ANALOG, ILOPROST, IN THE RAT

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (5) , 645-651
Abstract
The metabolic pathway of the stable prostacyclin analog, iloprost (ZK 36374) [a vasodilating and antiplatelet agent], was studied in the rat, both in vivo and in vitro by a rat liver perfusion model. Metabolites were isolated from both experiments by preparative high performance liquid chromatography and identified by GC/MS [gas chromatography/mass spectrometry] and NMR analysis. In vitro, iloprost was metabolized by consecutive .beta.-oxidation of the upper side chain. Both dinor-and tetranoriloprost could be isolated from the perfusion medium. The metabolic pattern in bile was similar to that in the perfusion medium. In vivo, iloprost was totally metabolized by .beta.-oxidation of the upper side chain and by subsequent hydroxylation and conjugation. The compounds identified in rat urine were tetranoriloprost, which represented about 3/4 of all metabolites, hydroxylated tetranoriloprost with the additional hydroxyl group presumably at position 17 and a conjugate of tetranoriloprost. Dinoriloprost and unchanged drug were not observed. .beta.-Oxidation of the upper side chain was stereoselective to give a 6.alpha.-H/6.beta.-H ratio of 86:14.