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Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance

Karel Allegaert1, Alain Rochette, Francis Veyckemans

  • 1Neonatal Intensive Care Unit, University Hospitals Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be

Paediatric Anaesthesia
|August 21, 2010
PubMed

Insights

Tramadol metabolism in infants shows complex interactions between age-dependent maturation and genetic factors. This can lead to varied drug effects due to differing rates of metabolite formation and renal elimination.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pediatric Pharmacology
  • Developmental Biology

Background:

  • Tramadol is metabolized to an active metabolite (M1) via CYP2D6, with M1 elimination occurring renally.
  • M1 formation depends on age-dependent CYP2D6 activity and genetic polymorphisms.
  • These metabolic and elimination pathways mature at different rates during infancy.

Purpose of the Study:

  • To investigate the interplay of ontogeny, genetic variations, and renal clearance in tramadol disposition during infancy.
  • To analyze the developmental pharmacokinetics of intravenous tramadol in neonates and infants.

Main Methods:

  • Pooled pharmacokinetic analysis of existing time-concentration data from neonates and infants.
  • Simulation of the effects of ontogeny, genetic polymorphisms, and renal elimination on tramadol pharmacokinetics.

Main Results:

  • Tramadol plasma concentration profiles vary significantly with postmenstrual age.
  • In 52-week-old infants, hepatic M1 formation clearance (CYP2D6) is mature, but renal elimination clearance is immature.
  • This immaturity in elimination can lead to higher M1 concentrations.

Conclusions:

  • Observed pharmacokinetic profiles may explain unexpected tramadol side effects in infants.
  • Maturational trends in drug elimination processes are relevant for other drugs like codeine.
  • Understanding these developmental pharmacokinetics is crucial for safe and effective pediatric drug use.
Abstract

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