Rimmer E M, Buss D C, Routledge P A, Richens A
Br J Clin Pharmacol. 1984 Jan;17(1):99-102. doi: 10.1111/j.1365-2125.1984.tb05007.x.
The plasma protein binding of phenytoin was investigated in 56 epileptic patients attending the outpatient clinic. The free phenytoin fraction was measured by equilibrium dialysis at 37 degrees C and the total concentration by a homogenous enzyme immunoassay technique. The free fraction ranged from 0.123 to 0.177 (median 0.144, mean +/- s.d. = 0.145 +/- 0.12). Distribution was consistent with normality. Four of the patients were also taking sodium valproate. The median free fraction of phenytoin in these patients was 0.174, 21% higher than that of the total group (P less than 0.05). The total concentration of phenytoin varied from 0.3 to 29.4 micrograms/ml (median 12 micrograms/ml, mean +/- s.d. = 13.31 +/- 6.13 micrograms/ml) and the free fraction was not related to the total drug concentration. There was a highly significant relationship between free phenytoin concentration and total phenytoin concentration (r = 0.986, P less than 0.001). There appears to be very little variability in protein binding of phenytoin in epileptic patients and thus total plasma phenytoin concentration closely reflects the free (unbound) drug concentration. Routine estimation of free plasma phenytoin concentration is therefore unnecessary and should be reserved for those patients where alteration in binding is likely, e.g. renal or hepatic disease or where adverse effects occur at unexpectedly low total phenytoin concentrations.
对56名到门诊就诊的癫痫患者的苯妥英血浆蛋白结合情况进行了研究。在37℃下通过平衡透析法测定游离苯妥英部分，并用均相酶免疫分析技术测定总浓度。游离部分范围为0.123至0.177（中位数0.144，均值±标准差=0.145±0.12）。分布符合正态性。其中4名患者同时服用丙戊酸钠。这些患者中苯妥英的游离部分中位数为0.174，比总体组高21%（P<0.05）。苯妥英的总浓度在0.3至29.4微克/毫升之间变化（中位数12微克/毫升，均值±标准差=13.31±6.13微克/毫升），且游离部分与总药物浓度无关。游离苯妥英浓度与总苯妥英浓度之间存在高度显著的相关性（r=0.986，P<0.001）。癫痫患者中苯妥英的蛋白结合似乎几乎没有变异性，因此血浆苯妥英总浓度密切反映游离（未结合）药物浓度。因此，常规估计游离血浆苯妥英浓度是不必要的，应仅用于那些可能发生结合改变的患者，例如肾脏或肝脏疾病患者，或在苯妥英总浓度意外较低时出现不良反应的患者。
