Naglo A S, Nergårdh A, Boréus L O
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
J Neurol. 1990 Jun;237(3):186-90. doi: 10.1007/BF00314592.
The intra-individual variation in plasma concentration of phenytoin was studied in ten clinically well controlled children on monotherapy. The drug concentration was determined in routine pre-dose samples taken on three to five different mornings. On two of these occasions, plasma phenytoin was also determined at 0.5, 1, 2, 3, 5 and 7 h after the dose. The difference between the highest and lowest morning concentrations in a patient varied between 7.5 and 40 mumol/l (mean 20.1 mumol/l). Half of all morning concentration values were lower than 40 mumol/l. This often-recommended lower limit for good seizure control should therefore be reconsidered. The two concentration versus time curves in each patient during 7 h after administration differed considerably in shape, and the first curve could not be used for prediction of the second curve. The ratio between unbound and total drug was very stable and amounted to 9.4, SD 0.94% (n = 168). It is concluded that the conventional single morning sample is satisfactory for routine monitoring in well-controlled children on monotherapy with phenytoin. In problem patients, and during combination therapy, however, more extensive investigation will be necessary, including repeated morning samples as well as determination of dose-interval curves and protein binding.
对10名接受单一疗法且临床控制良好的儿童，研究了苯妥英血浆浓度的个体内差异。在三到五个不同早晨采集的常规给药前样本中测定药物浓度。在其中两次采样时，还在给药后0.5、1、2、3、5和7小时测定血浆苯妥英浓度。患者早晨最高和最低浓度之间的差异在7.5至40μmol/L之间（平均20.1μmol/L）。所有早晨浓度值的一半低于40μmol/L。因此，应重新考虑这个经常被推荐的良好癫痫控制的下限。给药后7小时内，每位患者的两条浓度-时间曲线在形状上有很大差异，第一条曲线不能用于预测第二条曲线。游离药物与总药物的比率非常稳定，为9.4，标准差0.94%（n = 168）。结论是，对于接受苯妥英单一疗法且临床控制良好的儿童，常规的单次早晨样本足以进行常规监测。然而，对于有问题的患者以及联合治疗期间，需要进行更广泛的研究，包括重复早晨采样以及测定给药间隔曲线和蛋白结合情况。
