COMPARATIVE DISTRIBUTION OF TRITIUM-LABELED DIHYDROMORPHINE BETWEEN MATERNAL AND FETAL RATS

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

Tritium-labeled dihydromorphine was administered subcutaneously to near-term pregnant Sprague-Dawley rats. One-half to 16 hours later the fetuses were removed and specimens were obtained for estimation of free and conjugated dihydromorphine in maternal and fetal brains, kidneys, and plasma.

Despite a lower maximum plasma level in the fetuses, the fetal brain level reached a peak which was 2.7 times the highest maternal brain level. The peak concentration in maternal brain was only about that of maternal plasma, but fetal brain levels followed plasma levels quite closely at early time periods. At later times fetal brain concentrations were higher than plasma concentrations; this relationship was not seen in maternal rats.

Conjugated dihydromorphine was found in maternal plasma, livers, and kidneys, and in fetal plasma and livers at all time periods. Significant amounts of conjugate were not found in maternal brains after doses of 1 mg/kg or 2 mg/kg, but a small quantity was detected after 4 mg/kg. Low concentrations of conjugate were found in fetal brains 2 hours and more after drug administration, but not before. The ratio of conjugated-free drug was lower in fetal than in maternal specimens.

Distribution of free and conjugated dihydromorphine did not appear to be greatly influenced by dose of the drug except that the proportion of conjugate in maternal plasma tended to decrease with increasing dose. Distribution of the drug did not differ significantly between pregnant rats and adult nonpregnant females.