Serum protein binding kinetics of phenytoin in monotherapy patients

Objectives: To determine the binding characteristics of phenytoin to serum proteins in the Japanese population and to compare these with those reported by other investigators. Method: Serum samples examined in the study were obtained from 72 patients (35 males, 37 females) receiving phenytoin monotherapy. The patients' ages ranged from 1 to 73 years (1-15 pears, 36 subjects; 16-44 years, 20 subjects; 45-64 years, 13 subjects; greater than or equal to 65 years, 3 subjects). Results: The in vivo population binding parameters of phenytoin to serum proteins and theoretical minimal unbound serum phenytoin fraction (fu) were determined using the Scatchard equation. The association constant (K) was 0.020 l/mu mol, while the total concentration of binding sites (n(Pt) was 556 mu mol/l. The number of binding sites per albumin molecule (n) was 0.85, while binding ability (n.K) was 0.017 l/mu mol. The fu was 0.083. The n.K is approximately 1.1 times higher in patients of Pospisil et nl. (26) (i.e. 0.0191 l/mu mol) than in all our patients. The association content is approximately 1 1 times higher in our study than in the in vitro study of Monks ef al. (23) (i.e. 0.0186 l/mu mol), while n is similar between the two studies. The fil in our patients is similar to the unbound serum phenytoin fraction in adult patients receiving phenytoin therapy reported by Richens (2) (i.e. 0.1). Conclusion: Our results suggest that there may be small differences in the binding characteristics of phenytoin to serum proteins between Japanese and non-Japanese subjects. The unbound serum fraction of phenytoin in our patients with epilepsy can be assumed to be relatively constant in the therapeutic concentration range of phenytoin.