Protein binding of valproic acid in Japanese pediatric and adult patients with epilepsy

The binding of valproic acid to serum proteins in pediatric and adult patients was studied. Serum samples were obtained from 48 Japanese pediatric patients with epilepsy (group A) and 48 Japanese adult patients with epilepsy (group B) receiving valproic acid monotherapy. The patients' age ranged from 1 to 15 years for the pediatric patients and from 18 to 44 years (group B-younger) and 45 to 63 years (group B-older) for the adult patients. The serum concentrations of total and unbound valproic acid were measured by fluorescence polarization immunoassay, and the unbound serum fraction of valproic acid was analyzed by ultrafiltration. The mean association constant, K, and total concentration of binding sites, n(P), were as follows: group A, K= 0.016 L/μmol, n(P)= 1077 μM; group B, K = 0.011 L/μmol, n(P) = 1365 μM; group B-younger, K = 0.013 L/μmol, n(P) = 1291 μM; and group B-older, K= 0.006 L/μmol, n(P) = 1827 μM. Significant differences between groups A and B were observed in the serum free fatty acid concentration and the serum concentration ratio of free fatty acids to albumin. However, no significant differences between the two groups were observed in the binding of valproic acid to serum proteins. Group A's serum concentration ratio of free fatty acids to albumin was significantly lower than in group B-older and was lower than in group B-younger. However, there were no significant differences in binding between group A and groups B-younger and B-older. The serum concentration of albumin was significantly higher in group B-younger than in group B-older. Consequently, there was a significant difference in binding between groups B-younger and B-older. The serum protein binding of valproic acid was similar in pediatric and adult patients with epilepsy, but binding characteristics differed between younger and older adults.