A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients
A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients
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DOI：
10.1111/j.1742-1241.2007.01660.x
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发表时间：
2008-02-01
影响因子：
2.6
通讯作者：
Runyan, J. D.
中科院分区：
文献类型：
--
作者：
Henney, H. R., III;Runyan, J. D.
目的：替扎尼定是美国批准使用的少数几种口服解痉药之一，其治疗指数较窄，通常会使患者难以获得最佳剂量。我们调查了已发表的文献，以获得潜在的替扎尼定剂量与药代动力学、药物安全性和有效性关系的数据，并提供实用的药物剂量建议。结果如下：描述替扎尼定剂量比例关系的主要研究数量有限，即使包括使用高于目前推荐剂量的研究或导致超治疗替扎尼定浓度的药物相互作用研究数据。讨论和结论：有大量证据表明，健康受试者和患者的血浆替扎尼定浓度与剂量呈线性相关，尽管受试者间存在高度变异性。最常见的不良事件和药效学效应与血浆浓度相关。患者间血浆替扎尼定浓度变异性大，治疗指数窄，这一临床意义使得有必要对患者进行个体化治疗。提供了替扎尼定给药和/或制剂之间转换的实用建议。
Aims: Tizanidine, one of the few oral antispastic therapies approved for use in the USA, has a narrow therapeutic index that can often make optimal patient dosing difficult. We surveyed the published literature for data on potential tizanidine dose relationships to pharmacokinetics, drug safety and effectiveness, as well as to provide practical drug dosing advice. Results: The number of primary studies that describe tizanidine dose proportionality relationships was somewhat limited, even when including studies that used doses above those currently recommended or data from drug-drug interaction studies that resulted in supra-therapeutic tizanidine concentrations. Discussion and conclusions: There is substantial evidence to show that plasma tizanidine concentrations are linearly related to dose in healthy subjects and patients, although there is a high degree of intersubject variability. The most common adverse events and pharmacodynamic effects are related to plasma concentrations. The clinical implications of the large interpatient variability in plasma tizanidine concentrations and its narrow therapeutic index make it necessary to individualise patient therapy. Practical advice on tizanidine dosing and/or switching between formulations is provided.