Iorio A, Agnelli G
Istituto di Medicina Interna e di Medicina Vascolare, Università di Perugia, Italy.
Clin Pharmacokinet. 1997 Feb;32(2):145-72. doi: 10.2165/00003088-199732020-00005.
The current treatment for deep vein thrombosis is a 5- to 10-day course of heparin followed by 3 to 6 months of oral anticoagulants. Both heparin and oral anticoagulants present a high inter- and intra-individual variability and require individualisation and monitoring of their dosage. The pharmacokinetic properties of heparin have been difficult to assess through the radiolabelling procedures typically used for many other drugs. This is partially a result of the heterogeneous nature of heparin. Thus, the pharmacokinetics of heparin are expressed in terms of its pharmacodynamic activity. Improved coagulation test methodology coupled with the incorporation of patient factors such as bodyweight, height, baseline coagulation status, pretreatment heparin sensitivity and heparin concentrations, can be used to improve the accuracy of heparin dosage determination. Computer-based systems are now available to assist clinicians in quantitating dosage requirements, estimating bleeding risks, and storing patient dose-response relationships for future therapy monitoring. Low molecular weight heparin products might improve our ability to control anticoagulant therapy because drug concentration, as well as the effect on the clotting system, will be more predictable in patients receiving these products. In addition, low molecular weight heparins produce a more consistent, predictable anticoagulant response, and clinicians have a new pharmacological tool which may readily lend itself to patient-controlled, home-based anticoagulant pharmacotherapy. Where pharmacokinetics and pharmacodynamics could contribute to the optimisation of warfarin treatment is in the initiation of treatment, the estimation of the dosage required, the methods for drug monitoring, the assessment of unusual responses and the avoidance of drug interactions. Traditional pharmaco kinetic methods have limited applicability to the optimisation of warfarin therapy because there is no direct relationship between drug concentration and therapeutic effect. However, a variety of simple or sophisticated computer-assisted methods have been developed to help clinicians in individualising and monitoring warfarin treatment. New therapeutic approaches, such as direct thrombin inhibitors and thrombolytic agents, could overcome some limitations of the standard heparin plus oral anticoagulation therapy.
目前治疗深静脉血栓形成的方法是先使用肝素进行5至10天的疗程，然后口服抗凝剂3至6个月。肝素和口服抗凝剂在个体间和个体内均存在较大差异，需要个体化给药并监测剂量。肝素的药代动力学特性很难通过通常用于许多其他药物的放射性标记程序来评估。这部分是由于肝素的异质性。因此，肝素的药代动力学是以其药效学活性来表示的。改进的凝血试验方法，结合患者因素，如体重、身高、基线凝血状态、肝素预处理敏感性和肝素浓度，可用于提高肝素剂量测定的准确性。现在有基于计算机的系统可协助临床医生定量给药需求、估计出血风险以及存储患者剂量反应关系以用于未来的治疗监测。低分子量肝素产品可能会提高我们控制抗凝治疗的能力，因为在接受这些产品的患者中，药物浓度以及对凝血系统的影响将更可预测。此外，低分子量肝素产生更一致、可预测的抗凝反应，临床医生有了一种新的药理学工具，它可能很容易适用于患者自控的家庭抗凝药物治疗。药代动力学和药效学有助于华法林治疗优化的方面包括治疗的起始、所需剂量的估计、药物监测方法、异常反应的评估以及药物相互作用的避免。传统的药代动力学方法在华法林治疗优化方面的适用性有限，因为药物浓度与治疗效果之间没有直接关系。然而，已经开发出各种简单或复杂的计算机辅助方法来帮助临床医生个体化和监测华法林治疗。新的治疗方法，如直接凝血酶抑制剂和溶栓剂，可能会克服标准肝素加口服抗凝治疗的一些局限性。
