Metabolic Fate of Losartan, a New Angiotensin II Receptor Antagonist. (3). Transfer into Fetus and Milk in Rats.

Abstract

The transfer of losartan into the fetus and milk was investigated after single oral administration of 14C-losartan at a dose of 10 mg/kg to pregnant and lactating rats, respectively.1. At 1, 8 and 24 hr after administration of 14C-losartan to 13-day pregnant rats, the whole-body autoradiography showed that no radioactivity was distributed to the fetus. Very low levels of radioactivity were detected in the fetus at 8 and 24 hr following administration to 18-day pregnant rats.2. The maternal tissues of 18-day pregnant rats had the highest levels of radioactivity at 1 hr after administration and thereafter, the radioactivity declined with time, whereas the radioactivity in fetal tissues reached its peak between 1 and 8 hr after dosing and remained virtually unchanged from 8 to 24 hr. At 24 hr after administration, the radioactivity levels in the fetal blood, liver and kidney, and in the whole fetus were higher than that in the maternal plasma. At 8 or 24 hr after dosing, the radioactivity in the fetus accounted for 0.01% of the administered dose, indicating a slow transfer of the radioactivity into the fetal tissues.3. Following oral administration of 14C-losartan to lactating rats on the 11th day after delivery, the radioactivity in the milk peaked at 8 hr after administration, indicating that the transfer of radioactivity into the milk is very slow. From 8 to 48 hr, the radioactivity in the milk declined similarly to that in plasma with a terminal t1/2 of approximately 16 hr. At 48 hr after dosing, the radioactivity level in the milk corresponded to 45% of the plasma concentration.