Free Plasma Fraction of Valproic Acid in Epileptic Patients

Abstract

Monitoring the total plasma concentration of valproic acid (TVA) has disadvantages, and free plasma concentration (FVA) monitoring has been suggested as an alternative. The free plasma fraction of valproic acid (FVA/TVA, FF) varies considerably. In this study, factors capable of modifying FF were investigated. The TVA and FVA were determined in 141 epileptic patients treated with long term valproic acid. Samples for the determination of FVA were obtained by ultrafiltration. TVA and FVA determinations were carried out by fluorescent polarisation immunoassay. FF values were significantly higher in the monotherapy subgroup than in the multi-therapy subgroup in both an all-patient group and a female group. In the all-patient group, age did not significantly influence the FF value; the same was true in the monotherapy subgroup. FF values increased significantly with dose in the all-patient group and in the mono- and multitherapy subgroups. FF values increased with TVA; this increase was significant in the all-patient group, but not in the mono- or multitherapy subgroups. A statistically significant correlation was obtained between FF and FVA, and the TVA-FVA correlation was also significant. It was concluded that FF has great interindividual variability, which is independent of age and whether the patient is receiving mono- or multitherapy, but is dose- and concentration-dependent.