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Fentanyl dosage for preterm infants suggested by a pharmacokinetic, -dynamic, and -genetic model

Maddlie Bardol1,2, Elisabeth Norman3,4, Hugo Lagercrantz5

  • 1Institute of Child Health, University College London, London, UK. Maddlie.bardol@pharmetheus.com.

Pediatric Research
|July 18, 2024
PubMed

Insights

Fentanyl dosing for preterm infants needs to consider maturation and genetic factors. A 2 µg/kg intravenous dose is suggested for painful procedures like intubation, with specific gene variants impacting fentanyl clearance.

Area of Science:

  • Neonatal pharmacology
  • Pharmacogenetics
  • Pain management

Background:

  • Fentanyl is frequently used for procedural pain in preterm infants.
  • Optimal fentanyl concentrations for this population remain undefined.

Purpose of the Study:

  • To investigate the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) of fentanyl in preterm infants.
  • To establish appropriate fentanyl dosing for painful procedures in this vulnerable group.

Main Methods:

  • A cohort of 25 preterm infants (gestational age 23.3-34.1 weeks) received fentanyl (0.5 or 2 µg/kg) before procedures.
  • PK/PD modeling was employed, incorporating pain scores (EDIN) and genetic polymorphisms in drug-metabolizing enzymes, transporters, and receptors.
  • Covariates such as weight and maturity were analyzed for their effect on fentanyl clearance.

Main Results:

  • A two-compartment PK model effectively described fentanyl concentrations, with weight and maturity influencing clearance.
  • Genetic variants in ABCC1 and ABCC3 transporters significantly affected fentanyl elimination, accounting for 15% of interindividual clearance variability.
  • A PK/PD model linked fentanyl concentration to the EDIN pain score.

Conclusions:

  • An intravenous fentanyl dose of 2 µg/kg is recommended for clearly painful procedures, such as intubation, in preterm infants.
  • Personalized fentanyl analgesia should incorporate infant maturation and genetic variations in opioid transporters (ABCC1, ABCC3) that influence drug elimination.
Abstract

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