Lee C, Coleman R W, Mungall D R
Veterans Administration Medical Center, Palo Alto, CA 94304.
Clin Pharm. 1987 May;6(5):406-12.
The predictive performance of a Bayesian computer program using prothrombin-time (PT) response data with and without warfarin plasma concentrations to forecast patients' PTs at the time of hospital discharge was evaluated. A log-linear pharmacokinetic-pharmacodynamic model was used to describe and predict warfarin dose response in patients recently started on warfarin sodium. Individual patients' pharmacodynamic variables relating warfarin concentration to clotting-factor synthesis were obtained by Bayesian nonlinear regression analysis. Pharmacokinetic values for warfarin clearance and volume of distribution were either calculated using nonlinear regression from measured plasma warfarin concentrations or estimated based on literature-derived population regression equations. Percent mean absolute prediction error (precision) and prediction error (bias) for PT predictions were compared among and between analysis methods that used only literature data to estimate PT response and methods that used zero to five PTs with or without warfarin plasma concentrations. Eleven women and eight men completed the study. Predictions after four days of warfarin therapy using PT measurements beginning after either the first or third warfarin dose were clinically useful regardless of whether warfarin concentrations were used in the predictions. Predictions using fewer than four PT measurements were imprecise and biased. The Bayesian method in this study provided good predictions of PTs immediately before hospital discharge based on warfarin dosing and PT response after either four or five days of therapy. The use of warfarin plasma concentrations in the pharmacokinetic-pharmacodynamic model used here appears unwarranted.
评估了一个贝叶斯计算机程序的预测性能，该程序使用有或没有华法林血浆浓度的凝血酶原时间（PT）反应数据来预测患者出院时的PT。采用对数线性药代动力学-药效学模型来描述和预测近期开始使用华法林钠治疗的患者的华法林剂量反应。通过贝叶斯非线性回归分析获得了将华法林浓度与凝血因子合成相关的个体患者药效学变量。华法林清除率和分布容积的药代动力学值要么通过对测得的血浆华法林浓度进行非线性回归计算得出，要么基于文献推导的群体回归方程进行估算。在仅使用文献数据估算PT反应的分析方法与使用零至五次PT（有或没有华法林血浆浓度）的分析方法之间，比较了PT预测的平均绝对预测误差百分比（精度）和预测误差（偏差）。11名女性和8名男性完成了该研究。无论预测中是否使用华法林浓度，在首次或第三次华法林剂量后开始使用PT测量进行四天华法林治疗后的预测在临床上都是有用的。使用少于四次PT测量的预测不准确且有偏差。本研究中的贝叶斯方法基于华法林给药以及治疗四天或五天后的PT反应，对出院前的PT提供了良好的预测。在此处使用的药代动力学-药效学模型中使用华法林血浆浓度似乎没有必要。
