Fig. (2).

Impact of epilepsy and age on CYP2C9 function. Epileptic seizures negatively influence CYP2C9 expression in patients (A) comparing to healthy subjects (B). CYP2C9 mRNA levels were determined in leukocytes that can reflect the hepatic CYP2C9 activity. More than half of the pediatric patients with epilepsy (44/76) expressed CYP2C9 at low level, whereas the ratio of CYP2C9 low expressers in healthy subjects was less than one fifth (15/113). Association between steady-state serum concentrations of valproate and CYP2C9-status was demonstrated in children (N=76) (C), but not in adults (N=47) (D). The serum concentrations normalized by the dose and the bodyweight were determined at least four weeks after the beginning of valproate therapy. Solid line means the median of the groups, while * means the significant difference (P<0.01). Abbreviations: mut: loss-of-function CYP2C9 allele (CYP2C9*2 or CYP2C9*3), Low: low CYP2C9 expressers, Normal: normal CYP2C9 expressers.