Studies on the metabolic fate of 15(R)-15-methylprostaglandin E<SUB>2</SUB> (Arbaprostil) in rats (IV): Blood level and excretion after administration of 15(S)-15-methylprostaglandin E<SUB>2</SUB>

Abstract

15(R)-15-Methylprostaglandin E2 (CU-83) is converted to its epimer (CU-83(S)) in gastric acid after oral administration. In this study, the blood level and excretion of radioactivity were investigated in rats after intravenous and oral administration of 3H-CU-83(S) at a dose of 25 μg/kg. After intravenous dosing, the peak blood concentration of radioactivity, of 25.74 ng eq./ml, was observed at 45 min. Thereafter, the concentrations of radioactivity area under the blood concentration-time curve (AUC) during 72 hr period after the dosing was 135.42 ng eq.·hr/ml. After oral dosing, the maximum concentration of radioactivity in blood was 4.10 ng eq./ml at 3 hr and then declined bi-exponentially with the following half-lives of 4.46 and 26.83 hr. AUC was 48.62 ng eq.·hr/ml for 72 hr. After intravenous dosing, excretion of radioactivity was 30.52 % of the dose in urine and 60.42 % in feces during 72 hr. After oral dosing, excretion of radioactivity was 40.34 % in urine and 69.24 % in feces within 72 hr.