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Published on: September 11, 2011

Optimizing pediatric dosing: a developmental pharmacologic approach

Gail D Anderson1, Anne M Lynn

  • 1Department of Pharmacy, University of Washington, Seattle, Washington 98195, USA. gaila@u.washington.edu

Pharmacotherapy
|May 30, 2009
PubMed

Insights

Pediatric drug dosing requires understanding age-related pharmacokinetic differences. Children may need higher weight-corrected doses for drugs metabolized by specific CYP450 enzymes (CYP1A2, CYP2C9, CYP3A4), while doses are similar for renal elimination.

Area of Science:

  • Pharmacology and Pediatrics
  • Drug Metabolism and Elimination
  • Clinical Pharmacokinetics

Background:

  • Physiologic differences between children and adults significantly impact drug pharmacokinetics.
  • Optimizing pediatric drug doses requires understanding age-related variations in bioavailability, volume of distribution, protein binding, hepatic metabolism, and renal elimination.

Purpose of the Study:

  • To analyze age-related pharmacokinetic differences in pediatric patients.
  • To provide insights for optimizing drug dosages in children based on elimination pathways.

Main Methods:

  • Systematic literature search of English-language studies on age and pharmacokinetics (1979-July 2008) using MEDLINE.
  • Mechanistic analysis focused on drugs with a single primary elimination pathway (renal or specific metabolic isoenzyme).
  • Evaluation of cytochrome P450 (CYP) isoenzyme activity and renal excretion pathways.

Main Results:

  • Children require higher weight-corrected doses than adults for drugs solely eliminated by CYP1A2, CYP2C9, and CYP3A4.
  • Weight-corrected doses are similar for children and adults for drugs eliminated renally or via CYP2C19, CYP2D6, NAT2, or UGTs.
  • Bioavailability of drugs with high first-pass metabolism is reduced in children for CYP1A2, CYP2C9, and CYP3A4 substrates.

Conclusions:

  • Age-specific pharmacokinetic differences necessitate adjusted pediatric dosing, particularly for drugs metabolized by specific CYP enzymes.
  • A pharmacokinetic approach allows rational prediction of age-related drug effects, even with limited specific data.
  • By age 5, drug bioavailability influenced by efflux transporters is expected to be similar in children and adults.

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