Pharmacokinetics and Pharmacodynamics of Morphine in Infant Monkeys

Abstract

We report the pharmacokinetics of morphine administered as intravenous boluses in newborn (less than 7 days) and 3- to 4-month-old macaque monkeys. Morphine was administered in a series of bolus doses until PaCO2 was elevated greater than 50 mm Hg. In newborns less than 7 days of age, a mean dose of 1.4 mg/kg was required (range 0.75-2.8 mg/kg), and in the 3-month-olds, a mean dose of 1.88 mg/kg was required (range 1.5-2.5 mg/kg). The respiratory effects measured by PaCO2 and respiratory rate did not correlate with declining serum or cerebrospinal fluid morphine levels. Both newborn and 3- to 4-month-old macaque monkeys show only mild respiratory depression after intravenous morphine, at serum concentrations as high as 300-400 ng/ml. Infant and young macaque monkeys appear to be less sensitive to the respiratory depressant effect of morphine than humans.