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O-demethylation of tramadol in the first months of life

Karel Allegaert1, J N Van den Anker, R Verbesselt

  • 1Neonatal Intensive Care Unit, Department of Paediatrics, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be

European Journal of Clinical Pharmacology
|November 12, 2005
PubMed

Insights

Neonates exhibit O-demethylation activity, with tramadol metabolism correlating with postmenstrual age (PMA). Genetic factors likely contribute to variability in this process during early life.

Area of Science:

  • Pharmacology
  • Neonatal Metabolism
  • Drug Biotransformation

Background:

  • O-demethylation is a key metabolic pathway for tramadol.
  • Understanding tramadol metabolism in neonates is crucial due to their immature enzyme systems.

Purpose of the Study:

  • To assess the in vivo O-demethylation activity of tramadol in neonates and young infants.
  • To investigate the correlation between O-demethylation activity and perinatal factors like postmenstrual age (PMA) and postnatal age (PNA).

Main Methods:

  • Simultaneous collection of plasma and urine samples over 24 hours following intravenous tramadol administration.
  • Quantification of tramadol (M) and O-desmethyltramadol (M1) using high-performance liquid chromatography.
  • Correlation analysis between metabolite ratios (M/M1) and perinatal characteristics (PMA, PNA).

Main Results:

  • O-demethylation activity was present in neonates, evidenced by detectable M1 levels.
  • A significant negative correlation was found between the plasma and urine M/M1 ratio and both PMA and PNA.
  • Postmenstrual age (PMA) was identified as the independent variable influencing O-demethylation activity.

Conclusions:

  • Tramadol O-demethylation occurs early in neonatal life.
  • While PMA is correlated, it only partially explains the variability in O-demethylation.
  • Genetic polymorphism likely contributes significantly to inter-individual differences in tramadol metabolism in neonates.
Abstract

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