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 t_1/2 of approximately 16 hr. At 48 hr after dosing, the radioactivity level in the milk corresponded to 45% of the plasma concentration.