The pharmacokinetics of a single dose of morphine was investigated in five term infants (gestational age 37-40 weeks) and eight preterm infants (gestational age 25-32 weeks). In the five term infants, median (range) volume of distribution at steady state (Vd beta) was 1758 (634-2700) ml/kg, plasma clearance (Cl) was 4.73 (1.75-6.61) ml/kg/min and terminal half-life (T1/2) was 224 (107-394) min. In the eight preterm infants, Vd beta was 2366 (1662-2876) ml/kg, Cl was 2.82 (1.88-6.60) ml/kg/min and T1/2 was 556 (248-834) min. No correlation was found between clearance and gestational age, but we found a significant negative correlation between T1/2 and gestational age. We conclude that there is considerable variation in the pharmacokinetic properties of morphine in both term and preterm newborn infants. Because of this variation, careful individual assessment of the clinical effect of therapy with morphine in newborn infants should be exercised.

Five lactating women who underwent surgery and were treated with morphine epidurally or IV/IM in the postoperative phase were included in the study. The morphine concentrations in plasma and breast milk were determined 0, 15, 30, 45, 60, 90, 120, 240, 360 and 480 min after drug administration by means of a specific radioimmunoassay for morphine. The milk-to-plasma ratio was 2.45 +/- 0.8 (mean +/- s.d.). The amount of morphine transferred by nursing is, even at the peak concentration of 500 ng/ml milk, small and will hardly cause respiratory depression or drowsiness in the child.

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