Mammary excretion and placental transfer of cis-malonato[4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]pla tinum(II) in rats

The mammary excretion and placental transfer of cis-malonato[(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II) (CAS 146665-77-2, SKI 2053R), a new potential anticancer agent, were investigated in the lactating or pregnant rats after a single intravenous administration of ¹⁴C-SKI 2053R (20 mg/kg, 100 μCi/kg). The radioactivity of the milk declined in a biexponential fashion with an initial half-life of 0.39 h and with a terminal half-life of 14.05 h in the lactating rats. The radioactivity of the milk was lower than that of plasma until 1 h after dosing, but was higher than that of plasma from 4 h after dosing. ¹⁴C-SKI 2053R was well distributed to most tissues including uterus and placenta in the pregnant rats, but the levels of radioactivity in the amniotic fluid and fetuses were markedly lower than that in the maternal plasma. Therefore, it is concluded that SKI 2053R scarcely passes the blood-placenta barrier, which was confirmed by the whole-body autoradiography study.