Effect of temperature on serum protein binding characteristics of phenytoin in monotherapy paediatric patients with epilepsy.

摘要

OBJECTIVES: To determine the effects of temperature on binding characteristics of phenytoin to serum proteins in paediatric patients with epilepsy. METHOD: Serum samples examined in the study were obtained from 41 paediatric patients (23 male, 18 female) with epilepsy on phenytoin monotherapy. Their age ranged from 1 to 15 years (mean +/- SD, 10;2 +/- 4;0 years). Protein binding of phenytoin was evaluated by ultrafiltration under current laboratory routine conditions (25 +/- 3 degrees C) or at a temperature of 37 degrees C. The in vivo binding parameters of phenytoin to serum proteins were determined using a binding equation derived from the Scatchard equation for a one-site binding model. RESULTS: Significant differences were observed in serum concentrations of unbound phenytoin at the two temperatures (P < 0;05). The mean association constant L/micromol (K) of phenytoin to serum proteins is 0.016 L/micromol at 25 +/- 3 degrees C and 0;009 L/micromol at 37 degrees C, while mean total concentration of binding sites (n(Pt)) seems to be similar between the two temperatures (682 micromol/L for 25 +/- 3 degrees C and 746 micromol/L for 37 degrees C). Significant differences were observed in binding characteristics of phenytoin to serum proteins for the different temperature conditions of ultrafiltration (P < 0;05). CONCLUSION: Our study confirms that binding affinity for phenytoin-serum protein interaction is approximately 44% lower at 37 degrees C than at 25 +/- 3 degrees C and consequently, binding potential (K.n(Pt)) is approximately 38% lower at 37 degrees C than at 25 +/- 3 degrees C.