Studies on the Metabolic Fate of NK-104, a New Inhibitor of HMG-CoA Reductase (3) : Foeto placental Transfer and Mammary Excretion after Oral Administration in Rats

Abstract

NK-104 is a very potent competitive inhibitor of HMG-CoA reductase. In this study, the transfer of radioactivity into the fetus and milk were investigated in pregnant and lactating rats after a single oral administration of ¹⁴C-NK-104 at a dose of 1 mg/kg. Whole body autoradiograms of rats on the 18th day of gestation showed a low distribution of radioactivity to amniotic fluid and fetus. On the 13th and 18th day of gestation, the levels of radioactivity in the placenta tissue were less than those in the maternal plasma. Therefore little radioactivity was transferred into the fetus, accounting for less than 36% of that in maternal plasma. The radioactivity in the milk reached a maximum level at 6 hr after administration to the lactating rats on the 14th day after delivery, being seven times higher than that in the maternal plasma. Although the composition of radioactivity in the milk consisted mostly of the unchanged NK-104, its concentration was below the detection limit at 48 hr.