Department of Cardiology, Jinhua Hospital of TCM Affiliated to Zhejiang University of Traditional Chinese Medicine, Jinhua, Zhejiang 321000, P.R. China.
Department of Cardiology, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China.
Mol Med Rep. 2018 Apr;17(4):6144-6149. doi: 10.3892/mmr.2018.8562. Epub 2018 Feb 6.
Warfarin is the most commonly used oral anti-coagulant in clinic practice. However, it is difficult to recommend the correct dosage due to its narrow therapeutic window. The aim of the present study was to verify the clinical value of the Lou type equation, using pharmacogenetics‑based warfarin dosing algorithms to appropriately predict the actual maintenance dose. A total of 87 Chinese Han patients who required treatment with warfarin were enrolled and randomly divided into the experimental and control groups. In the experimental group, the first 3 doses of warfarin were calculated according to the Lou type equation. While in the control group, these 3 treatments were performed following the doctors' recommendations. Then the dose of warfarin was gradually adjusted to the stable dose according to the changes in the international standardized ratio. At the end of the 50 day experimental period, there were a greater number of patients in the experimental group who exhibited a stable blood concentration of warfarin than those in the control group (83.35 and 64.4%, respectively). In addition, the mean and median times for patients to obtain a stable dose in the experimental group were significantly shorter than those in the control group (mean, 18.2±1.7 and 27.3±2.0 days; and median, 11.7±1.1 and 20.5±1.8 days, respectively). The adverse reaction rate of the experimental group (9.5%) was markedly lower than that of the control group (26.7%). The occurrence of adverse reactions in the experimental group was also significantly later when compared with the control group (43.9±1.6 and 38.6±1.5 days, respectively). Furthermore, there was no significant difference between the average predicted dose (3.4±1.1 mg/day) and the average actual dose (3.5±1.4 mg/day; P=0.313). In conclusion, using the Lou type warfarin pharmacokinetic dosing algorithm equation to administer warfarin markedly shortened the adjustment time of warfarin to reach a stable dose and reduced the adverse reactions rate, thus supporting clinical feasibility.
华法林是临床实践中最常用的口服抗凝剂。然而，由于其治疗窗较窄，难以推荐正确的剂量。本研究的目的是验证基于遗传药理学的华法林给药算法的临床价值，以适当预测实际维持剂量。共纳入 87 例需要华法林治疗的汉族中国患者，并随机分为实验组和对照组。实验组的前 3 剂华法林根据 Lou 型方程计算。而在对照组中，这 3 次治疗均按照医生的建议进行。然后根据国际标准化比值的变化逐渐调整华法林的剂量至稳定剂量。在 50 天的实验期结束时，实验组中有更多的患者表现出稳定的华法林血药浓度（分别为 83.35%和 64.4%）。此外，实验组获得稳定剂量的平均和中位数时间明显短于对照组（平均 18.2±1.7 和 27.3±2.0 天；中位数 11.7±1.1 和 20.5±1.8 天）。实验组的不良反应发生率（9.5%）明显低于对照组（26.7%）。实验组不良反应的发生时间也明显晚于对照组（分别为 43.9±1.6 和 38.6±1.5 天）。此外，平均预测剂量（3.4±1.1mg/d）与平均实际剂量（3.5±1.4mg/d）之间无显著差异（P=0.313）。总之，使用 Lou 型华法林药代动力学给药算法给予华法林，明显缩短了华法林达到稳定剂量的调整时间，降低了不良反应发生率，支持临床可行性。
