Is Morphine Clearance Predictable in Humans?

Objectives: To evaluate pharmacokinetic models for prediction of morphine doses from premature neonates to adults.

Design: External evaluation of published models for morphine clearance by comparison with literature reports of morphine clearance in individual patients and healthy subjects.

Main Outcome Measures: Prediction of morphine dose rate in premature neonates, full term neonates, infants, children and adults.

Results: A previously described theory-based allometric model (1)using weight combined with a sigmoid maturation model using post-menstrual age successfully predicted the morphine dose rate (within 25% of target) in all age groups except infants (predicted dose 30% under target (95% CI 7-46%). Other published models based on empirical allometric scaling all made unacceptable predictions (>100% of target) in at least one age group(2-4).

Conclusions: Theory based allometric scaling combined with a maturation function has been prospectively confirmed to provide a sound basis for describing clearance and predicting doses in humans of all ages.

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  2. Mahmood I. Evaluation of a morphine maturation model for the prediction of morphine clearance in children: How accurate is the predictive performance of the model? Br J Clin Pharmac. 2011;71(1):88-94.
  3. Wang C, Peeters MYM, Allegaert K, Tibboel D, Danhof M, Knibbe CAJ. Scaling clearance of propofol from preterm neonates to adults using an allometric model with a bodyweight-dependent maturational exponent PAGE. 2010;19(Abstr 1818).
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