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华法林个体化剂量:重新配制以实现更合适的治疗和更好的依从性。

Warfarin Personalized Dosage: Re-compounding for a More Suitable Therapy and Better Compliance.

作者信息

Pellagatti Tommaso, Ternelli Marco, Frascio Davide, Bettini Ruggero

机构信息

Department of Pharmacy, University of Parma, Parma, Italy.

Farmacia Ternelli Dr. Maurizio, Bibbiano, RE, Italy.

出版信息

Int J Pharm Compd. 2017 May-Jun;21(3):247-250.

Abstract

Warfarin is still the most prescribed oral anticoagulant prescribed for the prophylaxis and treatment of thromboembolic events such as stroke, heart attack, embolism, and deep vein thrombosis. It is administered orally in the form of sodium salt as a tablet with a typical strength of 5 mg. The molecule has a narrow therapeutic index. As a consequence, the dosage must be individualized for each patient based on the patient response in terms of time of coagulation. Thus, warfarin represents an example of a drug whose dose needs to be tailored to individual requirements that are often changing and, therefore, constitute a paramount illustration of personalized medicine. The aim of the present work was to investigate to what extent the manual division of a warfarin tablet by the patient represents an issue in terms of dose accuracy and precision. A second goal was to demonstrate that possible problems stemming from the manual division of the warfarin tablet could be overcome by compounding a solid dosage form (e.g., a capsule) starting from the commercially available warfarin product. The results of the present study put into evidence the great inhomogeneity and discrepancy from the target dose obtained when commercially available warfarin tablets are manually divided in four parts. This represents a potential source of inefficacy of the anticoagulant activity, with increased risk of either bleeding or thromboembolic events. The proposed solution is effective and yet simple and economically affordable, in particular considering the cost of the possible hospitalizations related to therapy failure.

摘要

华法林仍然是预防和治疗血栓栓塞事件(如中风、心脏病发作、栓塞和深静脉血栓形成)最常用的口服抗凝剂。它以钠盐形式口服,制成片剂,典型强度为5毫克。该分子的治疗指数较窄。因此,必须根据每个患者在凝血时间方面的反应来个体化给药剂量。因此,华法林是一种需要根据经常变化的个体需求调整剂量的药物的例子,因此,它是个性化医疗的一个重要例证。本研究的目的是调查患者对华法林片剂进行手动分割在剂量准确性和精密度方面的问题程度。第二个目标是证明,通过从市售华法林产品开始配制固体剂型(如胶囊),可以克服华法林片剂手动分割可能产生的问题。本研究结果表明,当将市售华法林片剂手动分成四部分时,会出现很大的不均匀性以及与目标剂量的差异。这是抗凝活性无效的一个潜在来源,会增加出血或血栓栓塞事件的风险。所提出的解决方案是有效、简单且经济实惠的,特别是考虑到与治疗失败相关的可能住院费用。

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