Serum protein binding kinetics of phenytoin in monotherapy patients
| Autor: | Kazunari Todaka, Yasuo Kodama, Yoshio Mitsuyama, Reizo Kanemaru, Shinya Shinozawa, Hirofumi Kodama |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Phenytoin medicine.medical_specialty Adolescent medicine.medical_treatment Population Epilepsy Pharmacokinetics In vivo Internal medicine medicine Humans Pharmacology (medical) Child education Aged Pharmacology education.field_of_study business.industry Albumin Infant Blood Proteins Middle Aged medicine.disease Blood proteins Anticonvulsant Endocrinology Child Preschool Anticonvulsants Female business Protein Binding medicine.drug |
| Zdroj: | Journal of Clinical Pharmacy and Therapeutics. 23:361-365 |
| ISSN: | 1365-2710 0269-4727 |
| DOI: | 10.1046/j.1365-2710.1998.00173.x |
| Popis: | 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; > or = 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 1/micromol, while the total concentration of binding sites (n(Pt) was 556 micromol/l. The number of binding sites per albumin molecule (n) was 0.85, while binding ability (n.K) was 0.017 l/micromol. The fu was 0.083. The n.K is approximately 1.1 times higher in patients of Pospisil et al. (26) (i.e. 0.0191 l/micromol) than in all our patients. The association constant 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/micromol), 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. |
| Databáze: | OpenAIRE |
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