School of Pharmacy, University of Otago, Dunedin, New Zealand.
School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Sci Rep. 2018 Aug 13;8(1):12041. doi: 10.1038/s41598-018-30516-4.
Warfarin dosing methods based on existing models for warfarin and the international normalised ratio (INR) give biased maintenance dose predictions at the upper and lower quantiles of dose requirements. The aim of this work is to propose a conceptually different approach to predict INR after warfarin dosing. Factor VII concentration was proposed as the principal driving force for the INR. The time to steady-state INR (t) was determined based on the INR response to changes in factor VII concentrations following warfarin initiation, and from this the steady-state INR (INR) was derived. The proposed method requires timed, paired blood samples of INR and factor VII. At different simulated warfarin dose rates, the prediction error associated with the proposed method was shown to be within clinically acceptable limits for both the t (±2 days) and INR (±0.2). The use of the method was demonstrated in two patients who were initiated with 5 mg of warfarin daily. The difference in predicted versus actual steady-state INR were 0.0 and -0.4. The proposed method represents a unique approach to predict the INR. It considers factor VII as the main driver for INR and provides valuable information about the time to steady state INR.
华法林剂量方法基于现有的华法林和国际标准化比值(INR)模型,在剂量需求的上下分位数处给出了有偏差的维持剂量预测。这项工作的目的是提出一种概念上不同的方法来预测华法林给药后的 INR。因子 VII 浓度被提议作为 INR 的主要驱动力。稳态 INR(INR)是根据华法林起始后因子 VII 浓度变化对 INR 的反应来确定达到稳态 INR 的时间(t),并由此得出稳态 INR。该方法需要定时采集 INR 和因子 VII 的配对血样。在不同的模拟华法林剂量率下,与所提出的方法相关的预测误差对于 t(±2 天)和 INR(±0.2)均在临床可接受的范围内。该方法在两名每天接受 5 毫克华法林起始治疗的患者中得到了验证。预测与实际稳态 INR 的差异分别为 0.0 和-0.4。所提出的方法代表了一种预测 INR 的独特方法。它将因子 VII 视为 INR 的主要驱动因素,并提供了关于达到稳态 INR 时间的有价值信息。