Beraprost sodium (TRK-100 : Sodium (±)-(1
R*, 2
R*, 3
aS-, 8
bS-)-2, 3, 3a, 8b-tetrahydro-2-hydroxy-1-[(
E)-(3
S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1
H-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/m
l, respectively), and then declined biphasically. AUC at a dose of 0.2mg/kg was 98.2 ± 23.7ng • hr/m
l, 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 C
max, and thus seemed to be a major metabolite of beraprost sodium.
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