MAMMARY EXCRETION AND PLACENTAL-TRANSFER OF MINOMETHYL)-2-ISOPROPYL-1,3-DIOXOLANE]PLATINUM(II) IN RATS

The mammary excretion and placental transfer of cis-malonato[4R, minom ethyl)-2-isopropyl-1,3-dioxolane]platinum(II) (GAS 146665-77-2, SKI 20 53R), a new potential anticancer agent, were investigated in the lacta ting or pregnant rats after a single intravenous administration of C-1 4-SKI 2053R (20 mg/kg, 100 mu Ci/kg). The radioactivity of the milk de clined 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 ra dioactivity of the milk was lower than that of plasma until 1 h after dosing, bur was higher than that of plasma from 4 h after dosing. C-14 -SKI 2053R was well distributed to most tissues including uterus and p lacenta in tile pregnant rats, but the levels of radioactivity in the amniotic fluid and fetuses were markedly lower than that in the matern al plasma. Therefore, it is concluded that SKI 2053R scarcely passes t he blood-placenta barrier, which was confirmed by the whole-body autor adiography study.