Эпилепсия и пароксизмальные состояния (May 2017)

THERAPEUTIC DRUG MONITORING OF ANTICONVULSANTS IN CHILDREN IN CLINICAL PRACTICE

  • M. V. Leonova,
  • M. A. Ivzhits,
  • I. F. Tischenkova,
  • L. L. Shteinberg

DOI
https://doi.org/10.17749/2077-8333.2017.9.1.026-034
Journal volume & issue
Vol. 9, no. 1
pp. 26 – 34

Abstract

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Objective. To study concentration of valproats in children with epilepsy, newborns and infants with episyndrome using therapeutic drug monitoring (TDM) in routine clinical practice. Materials and methods. 75 children aged 1-18 years and 59 preterm newborns aged 0-90 days receiving valproic acid drugs were included in the study. Valproic acid concentration was measured using high performance liquid chromatography (HРLC). Results. Therapeutic concentration was achieved in 77.3% of children aged 1-18 years with an average daily dose of 25.94 mg/kg (1021.4 mg); overtherapeutic concentrations were registered in 9.3% of the cases. Concentration of valproic acid tended to decrease along with children’s age. Among children aged 1-18, a direct correlation between the daily dose (in mg/kg) and concentrations of valproates was observed: r=0.42 for Cmin and r=0.50 for Cmax. There was no correlation between age and concentration. In newborns, therapeutic concentration was achieved only in 33.9% of the cases with an average daily dose of 43.4 mg/kg (82.6 mg); overtherapeutic concentrations were registered in 11.9% of the cases. Significant differences in average daily doses and concentrations of valproic acid were found in newborns under 1 month of age; overtherapeutic concentrations in the group of preterm newborns under 1 month were observed in 23.5% of the cases versus 9.5% in the group of newborns of 2-3 months of age (p=0.07). Weak inverse correlation between age and concentration of valproic acid was seen in newborns: r=-0.25 for Cmin and r=-0.24 for Cmax. There was no correlation between the dose and concentration of valproic acid, this explains unpredictability of the dose response in the group of preterm newborns and low rates of achieving therapeutic concentrations. Conclusion. Specific features of valproic acid pharmacokinetics in newborns and children are associated with specific TDM parameters identified within the study; these findings show high value of TDM.

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