Pharmacokinetics and Pharmacodynamics of Morphine in Infant Monkeys

Abstract

We report the pharmacokinetics of morphine administered as intravenous boluses in newborn (<7 days) and 3- to 4-month-old macaque monkeys. Morphine was administered in a series of bolus doses until Pa(CO(2)) was elevated > 50 mm Hg. In newborns < 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 Pa(CO(2)) 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.

An interview with Dr. Anne Marie Lynn, a pioneering woman in medicine

“…Protein binding of morphine was 11% in newborns, and 17% at 1 year of age,” which may allow more “free” morphine to cross the blood‐brain barrier. She concluded that “increased CSF morphine is a transient finding in infant macaques, which appears to reach young adult values by 1 month of age.” 15,16 …”

“…She concluded that "increased CSF morphine is a transient finding in infant macaques, which appears to reach young adult values by 1 month of age." 15,16 Ultimately, if opioids were to gain widespread use in pediatric clinical practice, safety had to be proven. Thus, Dr. Lynn asked, "Are infants and newborns sensitive or resistant to morphine-related respiratory depression"?…”