Premium
Serum protein binding kinetics of phenytoin in monotherapy patients
Author(s) -
Kodama Hirofumi,
Kodama Yasuo,
Shinozawa Shinya,
Kanemaru Reizo,
Todaka Kazunari,
Mitsuyama Yoshio
Publication year - 1998
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1046/j.1365-2710.1998.00173.x
Subject(s) - phenytoin , free fraction , albumin , population , binding site , medicine , plasma protein binding , endocrinology , anticonvulsant , serum albumin , chemistry , in vivo , pharmacokinetics , pharmacology , biology , biochemistry , epilepsy , microbiology and biotechnology , environmental health , psychiatry
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 years, 36 subjects; 16–44 years, 20 subjects; 45–64 years, 13 subjects; ≥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/μmol, while the total concentration of binding sites ( n ( Pt ) was 556 μmol/l. The number of binding sites per albumin molecule ( n ) was 0·85, while binding ability ( n · K ) was 0·017 l/μmol. The fu was 0·083. The n · K is approximately 1·1 times higher in patients of Pospíšil et al . (26) (i.e. 0·0191 l/μmol) than in all our patients. The association contant is approximately 1·1 times higher in our study than in the in vitro study of Monks et al . (23) (i.e. 0·0186 l/μmol), while n is similar between the two studies. The fu 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.