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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >The anomalous pharmacokinetics of amiodarone explained by nonexponential tissue trapping.
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The anomalous pharmacokinetics of amiodarone explained by nonexponential tissue trapping.

机译：胺碘酮的异常药代动力学可以通过非指数组织捕获来解释。

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摘要

Conventional pharmacokinetic (PK) concepts fail to describe the long-term pharmacokinetics of the extremely cationic amphiphilic drug amiodarone. A nonclassical model based on the phenomenon of trapping at tissue binding sites with very long release times is presented, which implies that a volume of distribution and a steady-state level cannot be defined. In agreement with clinical PK data available in the literature, the model well describes not only single-dose disposition curves but also the persistently increasing plasma concentration-time curve during long-term treatment (up to 5 years) and the washout curve following cessation of therapy. The novel aspect is a long-tailed tissue residence time distribution which is incorporated into a recirculatory model leaving the initial distribution process and the clearance concept unchanged. The underlying theoretical approach, which is known as "strange or anomalous" kinetics in physical sciences, and the fractal scaling property of the model may enhance our understanding of the PK of extremely hydrophobic xenobiotics.
机译：常规药代动力学（PK）概念无法描述极阳离子两亲药物胺碘酮的长期药代动力学。提出了一种非经典模型，该模型基于在组织结合位点处捕获且释放时间非常长的现象，这意味着无法定义分布量和稳态水平。与文献中可获得的临床PK数据一致，该模型不仅描述了单剂量配置曲线，而且还描​​述了长期治疗（长达5年）中血浆浓度-时间曲线持续增加以及停止使用后的洗脱曲线。治疗。新颖的方面是长尾组织停留时间分布，该分布被纳入再循环模型中，而初始分布过程和清除率概念均保持不变。基础理论方法（在物理科学中被称为“奇怪或异常”动力学）和模型的分形缩放特性可能会增强我们对极疏水异源生物的PK的理解。

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