Fluorescence polarization immunoassay and enzyme immunoassay compared for free valproic acid in serum ultrafiltrates from epileptic patients.

Valproic acid (VPA; Depakene#{174}; Depakote#{174}) is indicated for use both as the sole and adjunctive therapy in the treatment of simple (petit mal) and complex absence seizures. It may also be used adjunctively in patients with multiple seizure types, which includes absence seizures. Adjustment of VPA dosage in patients with convulsive disorders is routinely guided by measurements of total VPA concentration-i.e., both free and protein bound-in sorum. Control of seizures reportedly is optimum when total concentrations of VPA in serum are 50 to 100 mg/L. However, the pharmacological activity of VPA is related to the concentration of the free component which-even in the absence of pathological conditions such as uremia, hypoalbuminemia, or drugs that compete with VPA for binding sites on protein-is widely variable (1). Abbott Diagnostics (North Chicago, IL) is in the process of introducing an assay for free valproic acid for use with their automated fluorescence polarization immunoassay in the TDx Analyzer. They hope this can be used to quantify free VPA in ultrafiltrate of serum. To evaluate this TDx system, I usedit to determine free VPA in serum from 47 patients and compared these results with values obtained by enzyme immunoassay (EMrr; Syva Co., Palo Alto, CA 94303). I also used the TDx to determine total serum VPA, compared the results with the results for free VPA concentrations, and calculated the variability of protein binding of VPA. I used samples from 47 patients (20 women, 27 men, mean age 25.6 years) selected for the study without conscious bias. All 47 patients had longfalling epilepsy, for which they were being treated as outpatients at the Epilepsy Center of Michigan. All patients were receiving VPA medication; 31 patients were also receiving phenytoin, 19 phenobarbital, 13 carbamazepine, four ethosuximide, and two primidone.