Studies on the metabolic fate of 15(R)-15-methylprostaglandin E2(Arbaprostil) in rats (V): Foeto-placental transfer and excretion into milk, and disposition after repeated administration

The distribution of radioactivity in the fetus and the excretion to the milk was studied following oral administration of 3H-15(R)-15-methylprostaglandin E2 (3H-CU-83) at a dose of 25 μg/kg to pregnant or lactating rats. The blood concentration, tissue accumulation and excretion of radioactivity were also examined during and after repeated oral administration of the compound at the same dose to male rats for 7 and 14 days. After oral administration to pregnant rats, very low radioactivity was detected in the tissues of fetus on day 19 of gestation. The blood level of radioactivity in the fetus was also lower than the maternal blood level and its ratio was about 0.08 times at 6 hr after administration. The radioactivity in milk reached the maximum level 2 hr after oral administration to lactating rats but was 0.23-0.72 times in comparison to that in the maternal blood level. The maximum blood concentration (Cmax) and the area under the blood concentration-time curve (AUC) for 24 hour period after single and final dosing of the 7 th and 14 th repeated administration were 3.17 ng eq./ml and 40.03 ng eq.·hr/ml, 3.41 ng eq./ml and 45.69 ng eq.·hr/ml and 2.97 ng eq./ml and 46.91 ng eq.·hr/ml, respectively. The concentrations of radioactivity in the plasma, blood and tissues after 7 th repeated administration of 3H-CU-83 were slightly higher than those after the single administration. The concentrations in the tissues after 14 th repeated administrations were similar to those after the 7 th repeated. Excretion of radioactivity in urine and feces was almost constant during 14 th repeated administration and was almost completed within 24 hr after the final administration.