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Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children

Natasa Djordjevic1, Slobodan M Jankovic2, Jasmina R Milovanovic1

  • 1Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica Street, 69, 34000, Kragujevac, Serbia.

European Journal of Drug Metabolism and Pharmacokinetics
|January 9, 2017
PubMed

Insights

Carbamazepine pharmacokinetics and pharmacogenetics in children are influenced by age, weight, genetics, and environment. Personalized dosing is crucial for safe and effective epilepsy treatment in pediatric patients.

Area of Science:

  • Pediatric Pharmacology
  • Clinical Pharmacy
  • Neuroscience

Background:

  • Carbamazepine remains a primary anticonvulsant for pediatric epilepsy.
  • Understanding its use in children requires examining pharmacokinetic and pharmacogenetic factors.

Purpose of the Study:

  • To review current knowledge on carbamazepine pharmacokinetics and pharmacogenetics in children.
  • To highlight factors influencing its efficacy and safety in this population.

Main Methods:

  • Systematic literature search of MEDLINE and SCINDEKS databases.
  • Review of studies on carbamazepine oral bioavailability, protein binding, volume of distribution, and clearance in children.
  • Analysis of pharmacogenetic associations (PXR, HNF4a, CYP1A2, ABCC2, PRRT2, HLA) with carbamazepine response.

Main Results:

  • Carbamazepine pharmacokinetics in children are age and weight-dependent, showing high variability due to dosing and co-medication.
  • Specific genetic markers (PXR*1B, HNF4a rs2071197, CYP1A2*1F, ABCC2 1249G>A, PRRT2 c.649dupC) are linked to carbamazepine pharmacokinetics or pharmacodynamics.
  • Human leukocyte antigen (HLA) typing is important for predicting adverse drug reactions.

Conclusions:

  • Both genetic and environmental factors significantly shape carbamazepine's pharmacokinetic and pharmacodynamic profile in children.
  • Tailoring carbamazepine dosage based on individual genetic and environmental influences is essential for optimizing treatment outcomes and ensuring patient safety.

Keywords:
CarbamazepineConventional TabletEpileptic ChildHuman Leukocyte AntigenStiripentol

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