药代动力学与药物分布研究的基本概况

Dudhat Kr
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引用次数: 0

摘要

危重患者表现出多种器官功能障碍,经常需要使用一系列药物治疗,如镇静剂、镇痛药、神经肌肉阻滞剂、抗生素、肌力药物和胃酸抑制剂。治疗这类患者的一个关键组成部分是了解器官功能障碍如何改变药物的药代动力学。由于胃肠功能衰竭,许多药物需要静脉注射。当口服途径是一种选择时,动力低下、肠道pH值变化和肠内喂养可能会影响生物利用度。影响药物清除率的主要因素是肝脏和肾脏功能障碍,从而影响患者的稳态药物浓度、疗效和毒性。许多药物主要是通过氧化代谢从体内清除的,人们越来越认识到,对于危重患者来说,肝细胞色素P450系统活性降低是多么重要。过滤和分泌清除途径都是消除母体药物及其活性代谢物所必需的,这使得肾衰竭同样至关重要。肾功能衰竭通常是导致稳态分布容积变化的次要原因,这会降低人体的有效药物浓度。内分泌、内皮、肌肉或中枢神经系统的衰竭也可能影响药物的代谢。对于某些药物,有强有力的证据表明药代动力学特征的变化取决于时间。为了最大限度地提高药效学反应和效果,了解危重病人的潜在病理生理,并利用药代动力学原理选择药物和给药方案是至关重要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Basic Aspects and the Overview on Pharmacokinetics and Studies on Drug Distribution- A Panoramic Review
Patients who are in critical condition display a variety of organ dysfunctions and frequently need to be treated with a range of medications, such as sedatives, analgesics, neuromuscular blockers, antibiotics, inotropes, and gastric acid suppressants. A crucial component of treatment for this patient population is comprehending how organ dysfunction might change the pharmacokinetics of medications. Due to gastrointestinal failure, many medications will need to be administered intravenously. When the oral route is an option, hypomotility, changes in gut pH, and enteral feeding may affect bioavailability. The main factors affecting medication clearance, and consequently steady-state drug concentrations, efficacy, and toxicity in a given patient, are hepatic and renal dysfunction. Many medications are cleared from the body primarily through oxidative metabolism, and it is becoming increasingly understood how important it is for critically ill patients to have diminished hepatic cytochrome P450 system activity. Both filtration and secretion clearance pathways are necessary for the elimination of parent medications and their active metabolites, making renal failure equally crucial. Renal failure is frequently a secondary cause of changes in the steady-state volume of distribution, which can lower the body's effective medication concentrations. Failure of the endocrine, endothelium, muscular, or central neurological systems may also have an impact on how a medication is metabolized. For some medications, there is strong evidence that changes in pharmacokinetic characteristics depend on time. To maximize the pharmacodynamic response and result, it is essential to understand the underlying pathophysiology in the critically sick and utilize pharmacokinetic principles in the selection of drug and dosing regimen.
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