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

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.