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Population pharmacokinetics of ketamine in children with heart disease

Mohammed H Elkomy1, David R Drover2, Gregory B Hammer2

  • 1Department of Anesthesia, 300 Pasteur Drive, Stanford University, Stanford, CA 94305-5640, USA; Department of Pharmaceutics and Industrial Pharmacy, Beni Suef University, Beni Suef, Egypt.

International Journal of Pharmaceutics
|December 3, 2014
PubMed

Insights

This study developed a population pharmacokinetic model for ketamine in pediatric cardiac patients to guide effective anesthesia. The model supports personalized dosing for children aged 1 year and older, ensuring anesthetic levels for 2 hours.

Area of Science:

  • Pharmacology
  • Pediatric Anesthesiology
  • Pharmacokinetics

Background:

  • Optimizing anesthetic medication in children with cardiac diseases is crucial for effective perioperative management.
  • Existing ketamine dosing regimens may not adequately account for age and cardiac function variations in pediatric patients.

Purpose of the Study:

  • To develop a population pharmacokinetic (PopPK) model for ketamine in children with cardiac diseases.
  • To establish a rationalized, personalized 2-hour anesthetic medication regimen based on cardiac function and age.

Main Methods:

  • A prospective, open-label study involving 21 children (6 months to 18 years) with cardiac diseases.
  • Intravenous ketamine administration (2 mg/kg) with blood sample collection over 8 hours for ketamine assay.
  • Pharmacokinetic data analysis using NONMEM software to describe ketamine disposition.

Main Results:

  • Ketamine pharmacokinetics was well-described by a two-compartment linear disposition model.
  • Population parameters included clearance and distribution volumes, normalized for weight.
  • Ketamine clearance in children with congenital heart disease was comparable to healthy subjects.

Conclusions:

  • A population pharmacokinetic model for ketamine in pediatric cardiac patients was successfully developed.
  • Computer simulations proposed a specific loading dose and infusion regimen to maintain anesthetic plasma levels for 2 hours in children ≥1 year.
  • The model provides a basis for personalized ketamine anesthesia in this vulnerable population.

Keywords:
ChildrenKetamineNONMEMPharmacokinetics

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