Studies on the metabolic disposition of timiperone. Feoto-placental transfer and excretion with milk of ¹⁴C-timiperone in rats

Abstract

Foeto-placental transfer and excretion with milk of ¹⁴C-timiperone was studied in the pregnant and lactating rats after a single oral administration of ¹⁴C-timiperone at a dose of 0.5 mg/kg. ³H-Haloperidol was also used as a reference compound.
1. On day 18 th of gestation, the concentration of radioactivity in the fetus 4 hr after administration of ¹⁴C-timiperone, was 1.7-1.8 times higher than that in the maternal blood, indicating that timiperone and its metabolites were easily transferred across the placenta to the fetus due to their lipophilicity.
In case of the feoto-placental transfer of ³H-haloperidol, much higher concentration of radioactivity in the fetus was observed, as compared with that of ¹⁴C-timiperone.
2. Following oral administration of ¹⁴C-timiperone to the lactating rats on day 10 th post partum, the milk levels of radioactivity increased gradually, and were 6.6-11.5 times higher than those in the maternal blood, indicating that timiperone and its metabolites were easily transferred to the milk from the blood.
On the contrary, in the ³H-haloperidol-treated lactating rats, the milk levels of radioactivity were almost the same as those in the maternal blood, showing low transfer of ³H-haloperidol and its metabolites to the milk.