Morphine in Fetuses after Maternal Injection: Increasing Concentration with Advancing Gestational Age

Pregnant rats were injected s.c. with [3H]morphine on Days 11, 13, 15, 17, and 19 of gestation. At ½, 1, 2, 6, and 12 hr after injection the fetuses were delivered by Caesarean section and were analyzed for [3H]morphine along with placentas and various maternal tissues. Very little morphine was found in the fetuses on Day 11. On each subsequent day until Day 17, the amount of morphine increased in the fetuses. On Day 19 the morphine in the fetuses was lower than on Day 17, possibly because of morphine metabolism by the placenta and fetus. Peak concentrations of morphine occurred in the fetuses at 1 to 2 hr after injection up to Day 15, while peaks occurred on Days 17 and 19 at 1 hr after injection. In addition, one group of pregnant animals was injected chronically with 10 mg/kg of morphine twice daily between Days 7 and 15 of gestation. On Day 15, these animals were injected with [3H]morphine and the fetuses analyzed at the times stated above. These fetuses showed a peak concentration at 1/2 hr after injection which was higher than the 1- to 2-hr peak in naive fetuses on the same day. In conclusion, these results show that morphine passes through the placenta more easily as gestation progresses and that the concentration of morphine in the fetuses can be altered by prior morphine exposure.