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

Abstract：

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.

journal_name

J Clin Pharm Ther

journal_title

Journal of clinical pharmacy and therapeutics

authors

Kodama H,Kodama Y,Itokazu N,Shinozawa S,Kanemaru R,Sugimoto T

doi

10.1046/j.1365-2710.2001.00340.x

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

175-9

issue

3

eissn

0269-4727

issn

1365-2710

pii

jcp340

journal_volume

26

pub_type

杂志文章

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