Graves N M, Leppik I E, Termond E, Taylor J W
Ther Drug Monit. 1986;8(4):427-33. doi: 10.1097/00007691-198612000-00009.
The saturable elimination kinetics of phenytoin (PHT) makes accurate dosing difficult. A simple equation has been derived to predict dosing requirements if one dose--steady-state serum concentration pair is known [new dose = first dose X Cpss (desired)0.2 X Cpss (achieved)-0.2]. This equation is based on an exponential relation between 177 pairs of PHT clearance and steady-state serum concentrations from 59 compliant patients. To evaluate this population clearance method (PCM), patients were drawn from two independent populations (Minnesota and Iowa, U.S.A.). Predicted doses obtained from PCM were compared with predictions from Bayesian, average Vmax, and average Km methods. The Bayesian method was the most precise and least biased of all methods, under- and overpredicting doses in equal frequency. PCM was biased to produce underpredictions. However, clinically achievable doses can be obtained by consistently rounding the calculated dose upward. The mean underprediction for the Bayesian method was 6 mg, for PCM 46 mg, for average Vmax 21 mg, and for average Km 11 mg. PCM is relatively precise, somewhat biased, and very easy to use.
苯妥英（PHT）的饱和消除动力学使得准确给药变得困难。如果已知一个剂量-稳态血清浓度对，则已推导了一个简单方程来预测给药需求[新剂量 = 首次剂量×Cpss（期望）^0.2×Cpss（实际达到）^ -0.2]。该方程基于来自59例依从性良好患者的177对PHT清除率与稳态血清浓度之间的指数关系。为评估这种群体清除率方法（PCM），从两个独立群体（美国明尼苏达州和爱荷华州）选取患者。将PCM得到的预测剂量与贝叶斯方法、平均Vmax和平均Km方法的预测结果进行比较。贝叶斯方法在所有方法中最为精确且偏差最小，预测剂量过低和过高的频率相同。PCM存在偏差，倾向于产生过低预测。然而，通过始终将计算出的剂量向上取整可获得临床上可达到的剂量。贝叶斯方法的平均过低预测为6 mg，PCM为46 mg，平均Vmax为21 mg，平均Km为11 mg。PCM相对精确，有一定偏差，且非常易于使用。
