Metabolism of Prostacyclin Derivative, Ataprost, in Rats

Abstract

Metabolism of ataprost [5(E)-15-cyclopentyl-6, 9-deoxa-6, 9α-methylene 16, 17, 18, 19, 20-pentanor-PGI₂, OP-41483], a prostacyclin derivative, was investigated in rats. After intravenous administration of [³H]ataprost, its metabolites in urine, bile and plasma were analyzed by TLC, and identified their structures by GC/MS spectrometry, ¹H-NMR spectroscopy and also co-chromatography with synthetic standards. The results were as follows:
1. The unchanged ataprost was not detected in urine and bile.
2. Ataprost was metabolized through oxidation of hydroxy group at C-15 position, reduction of double bond, consecutive β-oxidation of aside chain, hydroxy lation of cyclopentane ring at C-18 position and glucuronidation.
3. The major metabolites thus identified in plasma, urine and bile were 13, 14-dihydro-2, 3, 4, 5-tetranor-15-oxo-ataprost (PM3), 13, 14-dihydro-18-hydroxy-2, 3, 4, 5-tetranor-15-oxo-ataprost (UM1 and UM2) and glucuronic acid conjugate of 2, 3, 4, 5-tetranor-ataprost (BM1), respectively.