title: Biotransformation of the stable prostacyclin analogue, iloprost, in the rat.
abstract: The metabolic pathway of the stable prostacyclin analogue, iloprost (ZK 36 374), 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 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.
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D016285:Iloprost; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011464:Epoprostenol; D016285:Iloprost