Placental transfer and distribution of pinazepam and its metabolite N-desmethyldiazepam in the maternal and fetal rabbit: effect of the stage of gestation.
The distribution of pinazepam and its metabolite N-desmethyldiazepam was studied in fetuses of New Zealand rabbits on the 20th and 27th day of pregnancy. The concentrations of both compounds were also measured in the maternal brain, liver and uterus. Pregnant rabbits were sacrificed at 0.5, 2, 4 and 12 h after intravenous administration of pinazepam (5 mg/kg). The concentrations of pinazepam and N-desmethyldiazepam in various biological specimens were measured by a specific gas-chromatographic procedure. Pinazepam and N-desmethyldiazepam rapidly crossed the placenta. In 20 day old fetuses, comparable concentrations of pinazepam were found in the liver, brain, heart, lungs and kidneys. In contrast, the liver of 27 day old fetuses accumulated pinazepam at concentrations higher than the other tissues. The hepatic extraction of pinazepam, already described in adult rabbits (1), develops prenatally. A preferential accumulation of pinazepam rather than N-desmethyldiazepam was also observed in the maternal uterus. In this tissue the concentrations of pinazepam were 5-10 times higher on the 27th rather than the 20th day of pregnancy. The stage of pregnancy influences the distribution pattern of pinazepam in rabbit fetuses and their mothers.
Pacifici
G M
GM
Department of General Pathology, Medical School, University of Pisa, Italy.
Cuoci
L
L
Placidi
G F
GF
D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D003975:Diazepam / Q000031:analogs & derivatives*; D005260:Female; D005865:Gestational Age; D008431:Maternal-Fetal Exchange; D003708:Nordazepam / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011817:Rabbits
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C010763:pinazepam; D003708:Nordazepam; D003975:Diazepam