Pharmacokinetics and biotransformation of beraprost sodium I: Plasma level profile of beraprost sodium in rat.

Abstract

Beraprost sodium (TRK-100 : Sodium (±)-(1R*, 2R*, 3aS-, 8bS-)-2, 3, 3a, 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta [b] benzofuran-5-butyrate) labeled with tritium was orally and intravenously administered to male and female rats to examine plasma level profile and metabolism.After oral administration at doses of 0.04, 0.2 and 1.0mg/kg to male rats, concentration of the unchanged drug achieved maxima at 10-30min (18.4 ± 11.4, 42.7 ± 15.9 and 220.5 ± 68.5ng/ml, respectively), and then declined biphasically. AUC at a dose of 0.2mg/kg was 98.2 ± 23.7ng • hr/ml, which accouted for 81% of AUC after intravenous injection at the same dose. In female rats, higher concentrations were observed than in male.Metabolites found in plasma were 2, 3-dinor-beraprost, 13, 14-dihydro-l5-oxo-beraprost and 13, 14-dihydro-2, 3-dinor-15-oxo-beraprost. Among the three metabolites, the 2, 3-dinor-beraprost showed the highest AUC and Cmax, and thus seemed to be a major metabolite of beraprost sodium.