Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, Mitsuyama Y
Department of Pharmacy, Miyazaki Medical College, Kiyotake, Miyazaki, Japan.
Am J Ther. 2000 Nov;7(6):359-63. doi: 10.1097/00045391-200007060-00004.
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.
本研究的目的是确定苯妥英（PHT）在成人中与血清蛋白的结合特性。将我们研究中PHT与血清蛋白的结合参数与其他研究者报道的PHT在体内或体外与血清蛋白的结合参数进行比较。研究中的血清样本取自36例接受PHT单药治疗的成年患者（17例男性，19例女性）。本研究共分析了43个稳态浓度。患者年龄范围为16至73岁（均值[标准差]，42.9[14.7]岁）。使用从Scatchard方程推导的公式确定PHT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PHT分数（fu）。缔合常数（K）为0.014 L×μmol⁻¹，而结合位点的总浓度（n（Pt））为754 μmol×L⁻¹。每个白蛋白分子的结合位点数（n）为1.16，而结合能力（n.K）为0.016 L×μmol⁻¹。fu为0.087。Pospísil和Perlík的PHT单药治疗患者的n.K约比我们所有患者高1.2倍（即0.0191 L×μmol⁻¹）。在Monks等人的体外研究中，缔合常数约比我们的研究高1.3倍（即0.0186 L×μmol⁻¹），而两项研究中的n相似。我们患者中的fu与Richens报道的接受PHT治疗患者的未结合血清PHT分数相似（即0.1）。我们的结果表明，体内和体外研究中PHT与血清蛋白的结合亲和力可能存在微小差异。在PHT的治疗浓度范围内，癫痫患者中PHT的未结合血清分数可假定为相对恒定。
