Valproic acid clearance in children with epilepsy.

Abstract

OBJECTIVE: To evaluate population pharmacokinetics and the relationship between plasma concentration and daily dose of valproic acid (VPA) in a homogeneous group of children with epilepsy. METHODS: One hundred and fifty-one steady-state VPA plasma level measurements were made in 62 children aged 8 months to 6 years who were receiving VPA monotherapy. RESULTS: The level:dose ratio increased with age, its mean value was 1.7 in children aged under 2 years, 2.1 in children aged 2.4 years and 3.3 in children aged 4.6 years. Weight-adjusted values of VPA clearance (Cl) decreased with increasing age. The Cl values in these three age groups were 24.5+/-12.4 ml/kg/h, 19.9+/-6.1 ml/kg/h and 12.7+/-3.0 ml/kg/h, respectively. The relationship between VPA clearance and age was: Cl (ml/kg/h)=47.6 x age (months)(-0.29), (r=-0.87). This equation allows the estimation of VPA plasma clearance on the basis of the child's age, within the range 8-72 months. Therefore, it can be used to establish the initial maintenance paediatric dose of VPA in monotherapy. CONCLUSION: The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children.