Abstract
Studies were done in rats on placental transfer and excretion into milk of 14C-BMY-28100 upon single oral administration. Studies on absorption, distribution and excretion of 14C-BMY-28100 were also done upon multiple dosing.
1. Fetal tissue concentration of the drug reached a maximum at 6 hours after dosing on day 18 of gestation. The highest concentration observed was only 0.56 μg equiv./g in fetal kidney; The transfer of radioactivity into the fetus was low. Similar results were obtained from whole body autoradiograms performed in rats on day 12 and day 18 of gestation.
2. Concentrations of radioactivity in milk reached a maximum of 0.60 μg equiv./ml at 1 hour after administration, and gradually decreased thereafter. The maximum concentration in milk was 10% of the plasma concentration measured at the same time.
3. In the multiple oral administration study, 24 hours blood levels of radioactivity rose progressively with each dose, and reached a level 3.8 times higher than that observed with single dosing by the final (21st) administration. Tissue concentrations were relatively high in aorta, kidney and large intestine as were found upon single administration. However, the ratios of these levels between multiple and single dosing were lower than those observed in blood; 1.7, 3.6 and 2.9 for aorta, kidney and large intestine, respectively. Urinary and fecal excretion were constant after the 2nd administration.
