Disposition of Intrapartum Narcotic Analgesics in Monkeys

Abstract

Maternal-fetal disposition and neonatal respiratory depressant effect of narcotic analgesics were studied by administration of meperidine (2 mg/kg, IV) or alfentanil (IV infusion, 0.1 mg/kg total dose) during labor in rhesus monkeys. Fetal/maternal plasma ratios were lower for alfentanil, the more highly protein-bound drug (fetal/maternal ratio 0.20 at birth versus 0.46 for meperidine). However, elimination of alfentanil was delayed in the neonate. Indeed, plasma concentrations of alfentanil increased during the first 2 postnatal hours, indicating a compartmental shift from tissues to circulation in the neonate. As regards respiratory depression, six of ten narcotic-treated monkeys had suboptimal (less than 60 breath/min) respiratory rates at birth. Respiratory rate was negatively correlated with cord vein normeperidine and meperidine levels; the strongest correlation was with normeperidine (r = -0.84, P less than 0.01). Neonatal normeperidine elimination in the postnatal period was prolonged, as has also been observed in humans. These studies serve as a basis for comparing the neonatal neurobehavioral effects of the two analgesics and support the use of the rhesus monkey as an animal model to further understanding of the effects of narcotic analgesics on neonatal respiration.