Maternal-fetal distribution of morphine and alfentanil in near-term sheep and rhesus monkeys.

Maternal-fetal distribution of the opiate agents morphine and alfentanil was studied in 3 near-term sheep and rhesus monkeys. Blood samples were obtained from maternal and fetal arteries for radioimmunoassay after placement of catheters under halothane anesthesia. Fetal-maternal ratios (F/M) of plasma morphine concentrations for sheep increased from 0.04 to 0.47 during the first hour after bolus IV injection of 200 micrograms/kg morphine. However, in monkeys, F/M values were considerably higher, increasing from 0.27 to 1.85. Indeed, values over 1.00, indicating higher drug concentrations in fetal than maternal plasma, were seen in two monkeys at 10 and 60 min time points. For alfentanil, a more lipid soluble but highly protein-bound drug, F/M values of plasma concentrations were similar in the two species ranging from 0.1 to 0.6 after injection of 250 micrograms/kg in sheep and 125 micrograms/kg in monkeys. Quantitation of morphine glucuronide, the principal metabolite of morphine and total morphine-like immunoactivity, suggested that morphine was metabolized more rapidly in monkey dams than in sheep, and that morphine glucuronide was more readily distributed to monkey than sheep fetus. These data suggest that morphine, but not alfentanil, transfers more readily from dam to fetus in near-term monkeys than in sheep.