Effect of different doses of valproic acid on the serum levels of total and free diphenylhydantoin.

Abstract

In the course of a large prospective study aimed at evaluating the efficacy of Valproic Acid (VPA) in persons with intractable seizures, six patients that were on a steady dose of diphenylhydantoin (DPH) were exposed to different steady doses of VPA. The changes observed in the serum levels of total, free, and percentage of free DPH are reported here. There were no consistent changes in the serum levels of total DPH, but when serum levels of DPH, obtained before VPA was added to the therapeutic plan, were considered, it was found that the total DPH decreased in those patients with the higher baseline levels while it increased in those with the lower baseline levels. There also was an increase in the absolute total and the percentage of free DPH in most instances. The data suggested that the changes occurred soon after VPA was added and remained constant in the same patient as long as the total dose of VPA did not change. The data also suggested that VPA most probably interfered through a dual mechanism, displacement of albumin-fixed DPH, and decreased liver clearance of DPH. The interpersonal variability was such that only broad generalizations are possible. There is a need to measure free DPH in patients on VPA.