Abstract
14C-Zolpidem hemitartrate, a new hypnotic drug, was given orally in a dose of 3.29mg/kg to pregnant and lactating rats and its transfer into the fetus and milk was studied. The results are summarized as follows.
1. After oral dosing to a rat on day 18 of gestation, the radioactivity in the fetus was lower than that in the maternal blood. The radioactivity in the fetal tissues declined rapidly, and no radioactivity was detected 48 hours after dosing.
2. The whole body autoradiograms of rats, which were given the 14C-labelled compound orally on days 13 and 18 of gestation, showed that the radioactivity in the fetus was lower than that in the maternal blood and that the distribution of radioactivity to the fetus was higher in the perinatal period than in the organogenic period.
3. Thirty minutes after oral dosing to lactating rats, the radioactivity in the milk reached a maximum of 267ng eq/ml, and then declined with a half-life of 4.9 hours up to 24 hours. The radioactivity levels in the milk were almost the same or lower than those in the plasma up to 4 hours after dosing, but were 1.1 ?? 1.8 times higher thereafter. The ratio of AUCm to AUCp, which was calculated from the concentrations of radioactivity in milk and plasma respectively, was about 0.65. This suggested that zolpidem and/or its metabolites were less easily transfered into the milk.
