MATERNAL AND FETAL DISTRIBUTION OF H³-DIHYDROMORPHINE IN THE TOLERANT AND NONTOLERANT RAT

¹ Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

Pregnant Sprague-Dawley female rats were made tolerant to dihydromorphine by initiating s.c. injections of 2 mg/kg (base) of drug, twice daily, 30 hours after breeding and increasing the dosage to 15 mg/kg. Control nontolerant pregnant animals were treated in an identical manner except that they were injected with saline. Fetuses were removed by cesarean section at intervals of one-half to four hours after s.c. injection of 7 mg/kg (base) of H³- dihydromorphine to the maternal rat on the 21st day of gestation. Maternal plasma levels of free H³-dihydromorphine were maximum in the one-half-hour samples of both tolerant and control animals. Although the mean level appeared somewhat lower in tolerant animals, the difference was not statistically significant. The three- and four-hour maternal plasma levels in tolerant animals were significantly lower than in the control group. Fetal plasma concentrations in tolerant animals were significantly lower than in control animals at one hour, but the relationship was reversed at three and four hours. Both maternal and fetal tissue samples showed similar trends, but few gave differences of statistical significance. Recovery of drug from the skin and muscle of the injection site in tolerant rats was always lower than in control animals.