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Evaluation of valproate effects on acylcarnitine in epileptic children by LC-MS/MS

Yoko Nakajima1, Tetsuya Ito, Yasuhiro Maeda

  • 1Department of Pediatrics and Neonatology, Nagoya City University, Graduate School of Medical Sciences, Mizuho-cho, Nagoya, Japan.

Brain & Development
|January 4, 2011
PubMed

Insights

Valproate (VPA) treatment in children can alter specific acylcarnitine levels, especially when combined with other antiepileptic drugs. These changes, including increased hexanoylcarnitine, do not appear to cause severe carnitine deficiency at typical VPA doses.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Pediatric Medicine

Background:

  • Valproate (VPA), a fatty acid, is metabolized via the β-oxidation pathway.
  • Previous research suggests VPA toxicity may stem from carnitine deficiency and inhibited mitochondrial β-oxidation.

Purpose of the Study:

  • To investigate the impact of VPA on carnitine and acylcarnitine levels in children.
  • To determine the relationship between acylcarnitines and VPA blood levels in patients on long-term VPA therapy.

Main Methods:

  • Serum samples analyzed from children (1-15 years) on VPA monotherapy (n=28), VPA polytherapy (n=23), and controls (n=23).
  • Acylcarnitines and isomers quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Main Results:

  • Elevated 3-hydroxyisovalerylcarnitine and valproylcarnitine detected in VPA-treated groups.
  • VPA polytherapy showed increased hexanoylcarnitine, C12, C14:1-carnitines, and long-chain acylcarnitine to free carnitine ratio compared to controls.
  • VPA monotherapy did not decrease free carnitine or increase long-chain acylcarnitines.
  • Blood VPA levels correlated positively with several long-chain acylcarnitines (hexanoylcarnitine, C12, C14:1, C16:1, C18:1).

Conclusions:

  • Long-term VPA treatment affects specific acylcarnitines in pediatric patients.
  • Concomitant use of other anticonvulsants potentiates these acylcarnitine changes.
  • Valproylcarnitine formation alone is insufficient to cause severe carnitine deficiency at therapeutic VPA doses.
Abstract

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