Valproic acid clearance in children with epilepsy.
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.


CONCLUSIONS
The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children.
Department of Pharmacy, Arnau de Vilanova Hospital, Valencia, Spain.
A
A
Sánchez-Alcaraz
M B
MB
Quintana
E
E
López
I
I
Rodríguez
D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014635:Valproic Acid