Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y
Department of Pharmacy, Miyazaki Medical College, Kyotake, Japan.
J Clin Pharm Ther. 1998 Oct;23(5):361-5. doi: 10.1046/j.1365-2710.1998.00173.x.
To determine the binding characteristics of phenytoin to serum proteins in the Japanese population and to compare these with those reported by other investigators.
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).
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 Pospísil 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).
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.
确定苯妥英在日本人群中与血清蛋白的结合特性，并与其他研究者报告的结果进行比较。
本研究中检测的血清样本取自72例接受苯妥英单药治疗的患者（35例男性，37例女性）。患者年龄范围为1至73岁（1 - 15岁，36例；16 - 44岁，20例；45 - 64岁，13例；≥65岁，3例）。
使用Scatchard方程确定苯妥英与血清蛋白的体内群体结合参数以及理论最小未结合血清苯妥英分数（fu）。结合常数（K）为0.020 1/μmol，而结合位点的总浓度（n(Pt)）为556 μmol/L。每个白蛋白分子的结合位点数（n）为0.85，而结合能力（n.K）为0.017 L/μmol。fu为0.083。Pospísil等人（26）研究中的患者其n.K约比我们所有患者高1.1倍（即0.0191 L/μmol）。我们研究中的结合常数约比Monks等人（23）的体外研究高1.1倍（即0.0186 L/μmol），而两项研究中的n相似。我们患者中的fu与Richens（2）报告的接受苯妥英治疗的成年患者的未结合血清苯妥英分数相似（即0.1）。
我们的结果表明，日本人和非日本人之间苯妥英与血清蛋白的结合特性可能存在微小差异。在苯妥英的治疗浓度范围内，我们癫痫患者中苯妥英的未结合血清分数可假定为相对恒定。
