Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment.

Steady-state pharmacokinetics of valproic acid (VPA) with or without other antiepileptic drug (AED) treatment were studied in 37 children. Children (N = 16) receiving multiple AED therapy had a higher clearance (23.5 vs 13.0 ml/hr/kg, P less than 0.001), larger volume of distribution (0.30 vs 0.22 L/kg, P less than 0.01), and shorter half-life (9.4 vs 12.3 hours, P less than 0.01) than did those (n = 21) receiving VPA only. Inverse correlations of age with clearance (R = -0.559, P less than 0.01) and apparent volume of distribution of VPA (r = -0.490, P less than 0.05) were observed in children receiving monotherapy. In determining the dose and dosing interval of VPA, consider a possible alteration in the pharmacokinetics relating to age and other concurrent AED therapy.