Oral rapid loading of valproic acid--an alternative to the usual saturation scheme?

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies. Due to its broad field of application and its good compatibility, VPA is one of the most frequently prescribed antiepileptic drugs (AED) worldwide. Previous studies have examined the safety and tolerability of rapid intravenous-loaded VPA in the treatment of epilepsy and status epilepticus, but rapid oral loading has not been evaluated in paediatrics systematically in the past. The standard titration scheme takes 10-14 days, some physicians prefer a slower titration of up to 4 weeks. At many institutes, especially children are treated as inpatients until the desired dosage is reached. This causes high costs to the health system and is very inconvenient for the families affected. We have developed a new loading scheme to achieve a therapeutic serum level on the third day of treatment, in order to minimize the time between the beginning of the therapy and reaching the therapeutic serum level. This is the first attempt at doing this with VPA for children with epilepsy.

Effects of valproic acid, carbamazepine, and phenobarbitone on the fatty acid composition of erythrocyte membranes in children.

PURPOSE: To investigate a possible relation between antiepileptic drugs (AEDs) and the fatty acid composition of membranes. METHODS: Fatty acid (FA) composition of erythrocytes was studied in children with epilepsy receiving AED monotherapy. Children taking valproate (VPA, n = 28), carbamazepine (CBZ, n = 17), or phenobarbitone (PB, n = 14) were compared with healthy controls (n = 25). FAs were measured by capillary-gas chromatography (GC-FID). RESULTS: Significant changes (p < 0.05) in the FA composition of membranes were found. In children treated with VPA, C13:0 was decreased (8.2 +/- 2% vs. 10.7 +/- 4% in controls) and C14:0 increased (1.4 +/- 0.5% vs.1 +/- 0.5% in controls). C17:0 again was reduced (9.9 +/- 4% vs. 13.2 +/- 6% in controls), whereas the long-chained acids were enhanced: C18:2n-6 (6 +/- 2.4% vs. 3.9 +/- 2.5% in controls), and C20:4n-6 (1.9 +/- 1.7% vs. 1.4 +/- 0.5% in controls). The nonidentified FAs also increased with VPA therapy: 2.5 +/- 0.8% versus 1.7 +/- 0.9% in controls. Children treated with CBZ showed only minimal changes of FA composition: C13:0 was decreased compared with controls (8 +/- 2% vs. 10.7 +/- 4%). No changes were seen in patients taking PB. The mean corpuscular volume (MCV) showed important differences between the study groups: MCV was 84.7 +/- 6.0 fl during VPA therapy (p < 0.001) and 85.7 +/- 4.1 fl with CBZ (p < 0.001). During PB, the MCV increased to 82.87 +/- 3.29 fl compared with controls (78.73 +/- 4.92 fl; p < 0.01). CONCLUSIONS: VPA therapy is associated with changes of the FA composition of membranes, which is not the case with PB therapy. The implications of this finding remain to be established.