A longitudinal study of valproate free fraction in the specific age group at greatest risk for febrile convulsions (children below 3 years).

The behavior of the free fraction of valproic acid (VPA) was evaluated during long-term treatment of 24 children (9-18 months of age) with febrile convulsions. A series of relevant hematological parameters was monitored for the entire observation period (12 months). VPA plasma levels ranged from 54.3 +/- 26 to 66.6 +/- 32.8 micrograms/ml. The unbound fraction of the drug was determined in tears, which has been shown to be the best practical indicator of the free portion of an anticonvulsant drug, and ranged from 5.1 +/- 4.0 to 6.1 +/- 4.3 micrograms/ml. The tear/plasma ratio (and hence the free/total ratio) ranged from 9.3 to 9.7, in agreement with literature data. No significant variations of VPA plasma and tear levels, and therefore of the tear/plasma ratios, were ever observed. The hematological data revealed no significant alterations during the entire observation time, although some of the variables did fluctuate. Side effects were mild and temporary. The present report indicates that VPA has no particular toxic effect in young children treated for the prevention of febrile convulsions.