Huang Y F, Upton R N
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Australia.
Biopharm Drug Dispos. 1993 Nov;14(8):647-58. doi: 10.1002/bdd.2510140802.
In many regional pharmacokinetic experiments and models, the anatomical boundaries of the heart and kidney are intrinsically assumed to be barriers for drug diffusion such that these organs can be represented as one or more compartments. To test this, an experimental preparation was developed in which the heart and kidney of anaesthetized sheep were surrounded with 0.9% saline. The rate of drug diffusion from the surface of the organs into the saline was examined during constant-rate i.v. drug infusions. It was found that the maximum clearances of lidocaine and procainamide into the pericardial saline were 10.3-11.6 and 0.6-2.1 ml min-1 respectively, and the values for the kidney were 0.3-0.6, 0.1-1.0 and 0.4-1.3 ml min-1, for lidocaine, procainamide, and meperidine respectively. These corresponded to calculated times of 4-481 min to reach the steady-state saline concentration depending on the drug and the organ. The steady-state ratio of the saline concentrations over the arterial blood drug concentrations usually ranged from 0.5-1.0. It is concluded that drugs can rapidly enter regions of low or no perfusion surrounding these organs, and that the concept of treating the heart and kidney as compartments may not be valid in certain 'worst-case' situations.
在许多区域药代动力学实验和模型中，心脏和肾脏的解剖边界本质上被假定为药物扩散的屏障，因此这些器官可被表示为一个或多个隔室。为了验证这一点，开发了一种实验制剂，其中将麻醉绵羊的心脏和肾脏用0.9%的生理盐水包围。在恒速静脉输注药物期间，检查药物从器官表面扩散到盐水中的速率。结果发现，利多卡因和普鲁卡因酰胺向心包盐水的最大清除率分别为10.3 - 11.6和0.6 - 2.1 ml·min⁻¹，而肾脏对利多卡因、普鲁卡因酰胺和哌替啶的清除率分别为0.3 - 0.6、0.1 - 1.0和0.4 - 1.3 ml·min⁻¹。根据药物和器官的不同，这对应于达到稳态盐水浓度所需的计算时间为4 - 481分钟。盐水浓度与动脉血药物浓度的稳态比值通常在0.5 - 1.0之间。得出的结论是，药物可迅速进入这些器官周围低灌注或无灌注的区域，并且在某些“最坏情况”下，将心脏和肾脏视为隔室的概念可能并不成立。
