Johno I, Kuzuya T, Suzuki K, Hasegawa M, Nakamura T, Kitazawa S, Aso K, Watanabe K
Department of Hospital Pharmacy, School of Medicine, Nagoya University, Japan.
Ther Drug Monit. 1988;10(1):39-44.
Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum protein was assessed by ultrafiltration, and total and free DPH concentrations were determined by fluorescence polarization immunoassay. A strong correlation existed between the total and free concentrations [r = 0.958, p less than 0.001, standard error of estimate (+/- 1 SY) = 0.214]. The mean value for the DPH free fraction was 8.9% (range 5.7-16.3%). The samples obtained from patients on combination therapy with valproic acid (VPA) showed a larger DPH free fraction and greater variation. Exclusion of the 16 samples from patients concomitantly taking DPH and VPA yielded a better correlation (n = 46, r = 0.983, p less than 0.001, +/- 1 SY = 0.145). The mean free fraction in the patients not taking VPA was 7.7% (range 5.7-9.0%). The effect of VPA on the protein binding of DPH was also studied by addition of the same antiepileptic drugs to normal human plasma; the results were similar to those obtained for epileptic patients. These findings suggest that the free DPH fraction can be predicted from the total concentration, even when the drug is coadministered with other antiepileptic drugs, the sole exception being VPA.
采集了28例正在接受苯妥英[二苯乙内酰脲（DPH）]治疗的小儿癫痫患者的62份血清样本，以研究血清总DPH浓度与游离DPH浓度之间的相关性。还研究了联合使用的抗癫痫药物对DPH蛋白结合的影响。通过超滤评估DPH与血清蛋白的结合，并通过荧光偏振免疫测定法测定总DPH浓度和游离DPH浓度。总浓度与游离浓度之间存在很强的相关性[r = 0.958，p <0.001，估计标准误差（±1 SY）= 0.214]。DPH游离分数的平均值为8.9％（范围5.7-16.3％）。从接受丙戊酸（VPA）联合治疗的患者中获得的样本显示出更大的DPH游离分数和更大的变异性。排除同时服用DPH和VPA的患者的16份样本后，相关性更好（n = 46，r = 0.983，p <0.001，±1 SY = 0.145）。未服用VPA的患者的平均游离分数为7.7％（范围5.7-9.0％）。还通过向正常人血浆中添加相同的抗癫痫药物来研究VPA对DPH蛋白结合的影响；结果与癫痫患者的结果相似。这些发现表明，即使该药物与其他抗癫痫药物联合使用，也可以从总浓度预测游离DPH分数，唯一的例外是VPA。
