Bϋdingen Fiona V, Gonzalez Daniel, Tucker Amelia N, Derendorf Hartmut
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA ; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA ; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Ther Adv Infect Dis. 2014 Feb 1;2(1):17-42. doi: 10.1177/2049936113519089.
The liver is a complex organ with great ability to influence drug pharmacokinetics. Due to its wide array of function, its impairment has the potential to affect bioavailability, enterohepatic circulation, drug distribution, metabolism, clearance, and biliary elimination. These alterations differ widely depending on the cause of the liver failure, if it is acute or chronic in nature, the extent of impairment, and comorbid conditions. In addition, effects on liver functions do not occur in a proportional or predictable manner for escalating degrees of liver impairment. The ability of hepatic alterations to influence PK is also dependent on drug characteristics, such as administration route, chemical properties, protein binding, and extraction ratio, among others. This complexity makes it difficult to predict what these effects have on drugs. Unlike certain classes of agents, efficacy of anti-infectives is most often dependent on fulfilling pharmacokinetic/pharmacodynamic targets, such as C/MIC, AUC/MIC, T, IC/EC, or T>EC. Loss of efficacy, or conversely, increased risk of toxicity may occur in certain circumstances of liver injury. Although important to consider these potential alterations and their effects on specific anti-infectives, many lack data to constitute specific dosing adjustments, making it important to monitor patients for effectiveness and toxicities of therapy.
肝脏是一个复杂的器官，对药物的药代动力学有很大影响。由于其功能广泛，肝脏损伤有可能影响生物利用度、肠肝循环、药物分布、代谢、清除和胆汁排泄。这些改变因肝衰竭的病因、是急性还是慢性、损伤程度以及合并症的不同而有很大差异。此外，对于不同程度的肝功能损害，肝功能的变化并非呈比例或可预测的方式发生。肝脏改变对药代动力学的影响还取决于药物特性，如给药途径、化学性质、蛋白结合率和提取率等。这种复杂性使得难以预测这些影响对药物的作用。与某些类型的药物不同，抗感染药物的疗效通常取决于达到药代动力学/药效学目标，如C/MIC、AUC/MIC、T、IC/EC或T>EC。在某些肝损伤情况下，可能会出现疗效丧失，或者相反，毒性风险增加。虽然考虑这些潜在改变及其对特定抗感染药物的影响很重要，但许多缺乏构成特定给药调整的数据，因此监测患者治疗的有效性和毒性很重要。
