Lam Y W, Banerji S, Hatfield C, Talbert R L
College of Pharmacy, University of Texas at Austin, USA.
Clin Pharmacokinet. 1997 Jan;32(1):30-57. doi: 10.2165/00003088-199732010-00002.
Normal renal function is important for the excretion and metabolism of many drugs. Renal diseases which affect glomerular blood flow and filtration, tubular secretion, reabsorption and renal parenchymal mass alter drug clearances and lead to the need for alterations in dosage regimens to optimise therapeutic outcome and minimise the risk of toxicity. Renal disease is increasing and the cost of care has risen progressively over the past decade. Part of these costs is related to inappropriate drug therapy and excessive drug use. Although there are a variety of methods for evaluating the various aspects of renal function, the most practical and commonly used clinical measure of renal function is estimated creatinine clearance (CLCR) as a marker for glomerular filtration. This is useful since alterations in drug clearance are proportional to alterations in CLCR, and this relationship is used as the basis for changing doses and dosage intervals for drugs which are largely renally excreted. Two populations, neonates and the elderly, are at risk of inappropriate drug dosage due to physiological changes in renal function. Estimated CLCR may not be the best method of evaluating renal function in these patients, and dosage regimens should be carefully considered. Renal insufficiency and concurrent drug therapy used in these populations can either increase or decrease drug absorption, depending on the particular agent. Drug distribution may be altered in renal insufficiency due to pH-dependent protein binding and reduced protein (primarily albumin) levels. Interestingly, renal disease may affect hepatic as well as renal drug metabolism; the exact mechanisms for these changes are not well understood. The most important quantitative pharmacokinetic change is excretion. Glomerular filtration and tubular process may both be affected but not to the same extent, and the type of renal disease may differentially affect filtration and excretion. Drug removal by dialysis is dependent on a number of factors, including the characteristics of a particular drug and the type of dialysis and equipment used. Therapeutic outcomes may be evaluated using end-points such as plasma concentrations, patient outcomes such as reduction in fever or negative cultures, and system-wide changes such as drug-use or laboratory-use patterns.
正常肾功能对于许多药物的排泄和代谢至关重要。影响肾小球血流和滤过、肾小管分泌、重吸收以及肾实质质量的肾脏疾病会改变药物清除率，从而需要调整给药方案以优化治疗效果并将毒性风险降至最低。在过去十年中，肾脏疾病不断增加，护理成本也在逐步上升。这些成本的一部分与不适当的药物治疗和药物过度使用有关。虽然有多种方法可用于评估肾功能的各个方面，但最实用且常用的肾功能临床指标是估算的肌酐清除率（CLCR），它作为肾小球滤过的标志物。这很有用，因为药物清除率的变化与CLCR的变化成正比，这种关系被用作调整主要经肾脏排泄药物剂量和给药间隔的依据。新生儿和老年人这两类人群由于肾功能的生理变化而面临药物剂量不当的风险。估算的CLCR可能不是评估这些患者肾功能的最佳方法，给药方案应仔细考虑。这些人群中存在的肾功能不全和同时进行的药物治疗可能会增加或减少药物吸收，具体取决于特定药物。由于pH依赖性蛋白结合和蛋白（主要是白蛋白）水平降低，肾功能不全时药物分布可能会发生改变。有趣的是，肾脏疾病可能会影响肝脏以及肾脏的药物代谢；这些变化的确切机制尚不清楚。最重要的定量药代动力学变化是排泄。肾小球滤过和肾小管过程可能都会受到影响，但程度不同，肾脏疾病的类型可能会对滤过和排泄产生不同的影响。透析清除药物取决于许多因素，包括特定药物的特性以及所使用的透析类型和设备。治疗效果可以使用血浆浓度等终点指标、发热减轻或培养结果阴性等患者结局指标以及药物使用或实验室使用模式等全系统变化指标来评估。
