Effect of temperature on serum protein binding characteristics of phenytoin in monotherapy paediatric patients with epilepsy.
OBJECTIVE
To determine the effects of temperature on binding characteristics of phenytoin to serum proteins in paediatric patients with epilepsy.


METHODS
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).


CONCLUSIONS
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.
Kodama
H
H
Department of Pharmacy, Miyazaki Medical College, Kiyotake-machi, Miyazaki 889-1692, Japan.
Kodama
Y
Y
Itokazu
N
N
Shinozawa
S
S
Kanemaru
R
R
Sugimoto
T
T
D000293:Adolescent; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D010672:Phenytoin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D011485:Protein Binding / Q000502:physiology; D013696:Temperature; D014462:Ultrafiltration
D000927:Anticonvulsants; D001798:Blood Proteins; D010672:Phenytoin