Valproic acid clearance in children with epilepsy
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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/kd/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%27s 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.
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/kd/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.
