PLACENTAL TRANSFER OF DIAZEPAM-¹⁴C IN MICE, HAMSTERS AND MONKEYS

Abstract

Twenty-five mice (13 in early pregnancy and 12 in late pregnancy), 8 hamsters in late pregnancy, and 4 third trimester pregnant Cynomolgus iris monkeys were injected with diazepam-¹⁴C and sacrificed at various time intervals. The maternal distribution, the placental transfer and the fetal distribution of diazepam-¹⁴C and its metabolites were studied by autoradiography and liquid scintillation counting. he unchanged diazepam-¹⁴C was distinguished from the diazepam metabolites by thinlayer chromatography. Diazepam-¹⁴C and its metabolites crossed the placental barrier and accumulated in the fetal tissue in all three of the tested species. In mice diazepam-¹⁴C and its metabolites accumulated in the fetuses more rapidly in late than in early pregnancy. Fetal monkeys had a high uptake of radioactivity in the peripheral nerves, liver, spinal cord, kidney, lung, fat, cerebellum and plasma. The pronounced uptake and long retention of diazepam and its metabolites in the fetal monkey cerebellum, spinal cord and peripheral nerves may explain the temporary hypoactivity and hypotonicity that has been reported to occur in human infants when their mothers receive diazepam during labor.