Serum albumin-adjusted phenytoin levels: an approach for predicting drug efficacy in patients with epilepsy, suitable for developing countries

Abstract

The antiepileptic drug phenytoin has a high degree of plasma protein binding. Therefore, total phenytoin levels in plasma are misleading indicators of clinical efficacy. This study was designed to investigate whether serum albumin-adjusted phenytoin levels in Indian patients with epilepsy predict clinical outcome better than total phenytoin levels. Fifty patients with epilepsy were included in the study and were followed-up for a period of 6 months. Serum albumin levels were estimated spectrophotometrically using the bromocresol green dye method, and serum phenytoin levels were estimated using high pressure liquid chromatography. Values were expressed as mean +/- SEM. Corrected phenytoin levels were calculated using the Sheiner-Tozer equation. Corrected phenytoin levels = Measured total phenytoin(micromol/l) [(albumin g/1 x 0.9)+ 0.1] 40. At Visit 1, mean serum albumin levels were 44.1 +/- 1.1 micromol/l and mean serum phenytoin levels were 33.9 +/- 2.8 g/l. After correction of the total phenytoin levels using the Sheiner-Tozer equation, 30% of the patients shifted to a different category. The follow-up visits showed similar results. Throughout the study, the corrected phenytoin levels were better indicators of clinical outcome than the total levels. In 23% of patients there was a significant difference between total and corrected phenytoin levels. In patients with serum albumin levels in the hyper- and hypoalbuminemic range, corrected phenytoin levels were better indicators of clinical outcome. In developing countries like India, where estimation of free drug levels is expensive and suitable equipment is not available in most centers, serum albumin-adjusted levels can be used by pharmacologists to predict response and thus assist in clinical decision-making.