Metabolism of 8-Chloro-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine (D-40TA), a New Central Depressant. IV. Placental Transfer and Excretion in Milk in Rats

Abstract

1. Placental transfer of [¹⁴C]D-40TA and [¹⁴C]nitrazepam was studied after intravenous injection to pregnant rats on the 14th and 20th days of gestation. In both stages of pregnancy, D-40TA and its 1-oxo metabolite freely crossed the placenta, their foetus/maternal blood concentration ratios 1 h after dosing being approximately 1. The corresponding ratios for nitrazepam were 0.3 in middle pregnancy and 0.7 in late pregnancy. Foetal levels of the two benzodiazepines were not significantly different, because of higher levels of nitrazepam in the maternal blood.

2. Radioactivity concn. was at all times highest in placenta and foetus, and lowest in amniotic fluid, both in middle and late pregnancy. Radioactivity in these tissues disappeared as maternal blood levels declined.

3. Autoradiography of rat foetuses in late pregnancy showed that, 1 h after injection of the mothers with the labelled compounds, relatively higher concns. were noted in the foetus adrenal, adipose tissue, liver and gastro-intestinal wall; uniform distribution was found in other tissues.

4. Radioactivity was detected in milk of rats given either [¹⁴C]D-40TA or [¹⁴C]nitrazepam intravenously, significantly higher concn. being seen with the latter compound.