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Age-dependent morphine partitioning between plasma and cerebrospinal fluid in monkeys
A M Lynn1, T I McRorie, J T Slattery
1Department of Anesthesiology, School of Medicine, University of Washington, Seattle.
Developmental Pharmacology and Therapeutics
|January 1, 1991
Summary
Newborn monkeys show higher morphine levels in cerebrospinal fluid (CSF) than older monkeys. This increased morphine penetration into CSF is transient, normalizing by one month of age.
Area of Science:
- Pharmacology
- Neuroscience
- Pediatric Medicine
Background:
- Morphine's distribution between blood and cerebrospinal fluid (CSF) is crucial for understanding its central nervous system effects.
- Age-dependent differences in drug partitioning may impact therapeutic efficacy and safety in pediatric populations.
Purpose of the Study:
- To evaluate the steady-state partitioning of morphine between blood and CSF in infant and young adult pigtailed monkeys.
- To investigate age-related changes in morphine's CSF to plasma ratio and its relationship with protein binding.
Main Methods:
- Assessed steady-state partitioning of morphine in pigtailed monkeys at three age groups: 2-3 days, 1 month, and 1 year.
- Determined protein binding of morphine to serum proteins using ultrafiltration.
Main Results:
- Newborn monkeys (2-3 days) exhibited a significantly higher CSF to plasma ratio for morphine (0.506) compared to 1-month-old (0.369) and 1-year-old (0.374) monkeys.
- Morphine protein binding was lower in newborns (11%) than in 1-year-old monkeys (17%), which did not account for the elevated CSF penetration in neonates.
- Increased CSF morphine levels in infant macaques were found to be transient, reaching young adult levels by 1 month of age.
Conclusions:
- Neonatal pigtailed monkeys demonstrate enhanced morphine penetration into the CSF compared to older individuals.
- The higher CSF morphine levels in newborns are not explained by differences in serum protein binding.
- Age-dependent changes in blood-brain barrier transport or other physiological factors likely contribute to the transient increase in CSF morphine observed in infant macaques.