Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA.
Curr Pharm Biotechnol. 2011 Dec;12(12):2030-6. doi: 10.2174/138920111798808211.
The complexity of managing critically ill patients has increased since the early establishment of intensive care units in the 1950s. Despite of the fact that the number of drugs available to clinicians has increased, the understanding of the pharmacokinetics of individual drugs in specific disease states is still a matter of concern. Among the pharmacokinetic processes which may be affected in this patient population, drug distribution is a very important one. Changes in drug distribution may cause inadequate drug exposure at the infection site and consequently influence clinical outcome. Since drug distribution is dependent on a plethora of factors, including the physicochemical characteristics of the drug, we will focus on the most common mechanisms responsible for altered tissue distribution. These include changes in protein binding, fluid shifts, and pH changes. Although less common, alterations in organ perfusion may also play a role, particularly in heart failure patients. Despite great advances in understanding the distribution of antibacterial drugs, further studies are needed to define the consequences of changed drug distribution in critically ill patients on dosing regimens and clinical outcome.
自 20 世纪 50 年代重症监护病房（intensive care unit，ICU）建立之初以来，危重症患者的管理复杂性不断增加。尽管可供临床医生使用的药物数量有所增加，但在特定疾病状态下，个体药物的药代动力学（pharmacokinetics）理解仍然是一个令人关注的问题。在可能受影响的药代动力学过程中，药物分布是非常重要的一个过程。药物分布的变化可能导致感染部位药物暴露不足，从而影响临床结局。由于药物分布取决于包括药物理化特性在内的众多因素，我们将重点关注导致组织分布改变的最常见机制。这些机制包括蛋白结合的改变、液体转移和 pH 值变化。尽管不太常见，但器官灌注的改变也可能起作用，尤其是在心力衰竭患者中。尽管在理解抗菌药物分布方面取得了重大进展，但仍需要进一步研究，以确定危重症患者药物分布改变对剂量方案和临床结局的影响。
