Placental transfer and mammary excretion of a novel angiotensin receptor blocker fimasartan in rats

초록

Background: Fimasartan (FMS) is a potent angiotensin receptor blocker for the treatment of mild to moderate hypertension. This study aimed to evaluate the transfer of FMS to fetus and breast milk in rats. Methods: In order to study the transfer to the fetus and nursing pup, pregnant and nursing maternal rats were administered with FMS by a constant intravenous infusion to reach target plasma concentrations of 200 ng/mL and 100 ng/mL. The concentrations of FMS in plasma, placenta, amniotic fluid, fetus, and milk were determined by a validated LC-MS/MS assay. Results: Upon constant intravenous infusion, the plasma FMS concentration reached the target steady state concentrations (C-ss = 200 ng/mL and 100 ng/mL) in 24 h. The tissue-to-plasma partition coefficients (K-p) for placenta, amniotic fluid, and milk were obtained based on the observed FMS concentrations in the tissues and C-ss. The K-p values for all tissues were not different between high (C-ss = 200 ng/mL) and low (C-ss = 100 ng/mL) dose groups. While the mean K-p of the placenta was 44.6-59.0 %, the mean K-p was 1.3-1.7 % for the amniotic fluid and 14.9-17.0 % for fetus. The mean K-p of milk was 10.4-15.2 %. Conclusions: Placental transfer and milk excretion of FMS was relatively lower compared to other angiotensin receptor blockers.

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