Studies on the Metabolic Fate of NZ-105 (II) : Transfer into the Fetus and Milk, and Absorption, Distribution, Metabolism and Excretion after Repeated Administration to Rats.

Abstract

Transfer of radioactivities into the fetus and milk after oral administration of ¹⁴C-NZ-105 to pregnant or lactating rats were studied. Absorption, distribution, metabolism and excretion of ¹⁴C-NZ-105 were studied in male rats after repeated oral administration (21 times) at the dose of 10mg, /kg/day.
1. On day 13 and 18 of gestation, the autoradiography revealed that the radioactivity in the fetus was very lower than that in the maternal blood. On day 18 of gestation, the radioactivity in the fetal blood and liver was lower than that in the maternal plasma.
2. Radioactivity level in the milk was similar to that of plasma but it disappeared below detection limit at 48hr after oral administration.
3. Blood levels of radioactivity at 24hr after daily dosing increased with the number of doses. Blood concentration at 24hr after the 21-st dose was 8 times higher than blood concentration at 24hr after the first dosing respectively.
4. After repeated administration, the radioactivities in most of tisuues at 24hr reached the steady state after the 14-th administration.
5. The cumulative excretion of radioactivity in urine and feces accounted for 2.8% and 97.5% of the total dose, respectively, within 120hr after the final administration.
6. The ratio of unchanged drug to its metabolites, measured as a fraction of total radioactivity in the plasma at 2hr after the last dosing was similar to that after the single dose.