In vivo binding characteristics of phenytoin to serum proteins in monotherapy for adults with epilepsy.

The aim of the present study was to determine the binding characteristics of phenytoin (PHT) to serum proteins in the adults. Binding parameters of PHT to serum proteins in our study were compared with in vivo or in vitro binding parameters of PHT to serum proteins reported by other investigators. Serum samples in the study were obtained from 36 adult patients (17 men, 19 women) receiving PHT monotherapy. A total of 43 steady-state concentrations were analyzed in the study. Patients' age ranged from 16 to 73 years (mean [SD], 42.9 [14.7] years). The in vivo population binding parameters of PHT to serum proteins and theoretical minimal unbound serum PHT fraction (fu) were determined using an equation derived from the Scatchard equation. The association constant (K) was 0.014 L x micromol(-1), whereas the total concentration of binding sites (n(Pt)) was 754 micromol x L(-1). The number of binding sites per albumin molecule (n) was 1.16, whereas binding ability (n.K) was 0.016 L x micromol(-1). The fu was 0.087. The n.K is approximately 1.2 times higher in PHT monotherapy patients of Pospísil and Perlík (ie, 0.0191 L x micromol(-1)) than in all our patients. The association constant is approximately 1.3 times higher in the in vitro study of Monks et al (ie, 0.0186 L x micromol(-1)) than in our study, whereas n is similar between the two studies. The fu in our patients is similar to the unbound serum PHT fraction in patients receiving PHT therapy reported by Richens (ie, 0.1). Our results suggest that there may be small differences in the binding affinity of PHT to serum proteins between in vivo and in vitro studies. The unbound serum fraction of PHT in epileptic patients can be assumed to be relatively constant in the therapeutic concentration range of PHT.