Brater D C
Drugs. 1980 Jan;19(1):31-48. doi: 10.2165/00003495-198019010-00003.
Renal function can modify the relationship between drug dose and clinical effect in a variety of ways. Effects on absorption, distribution volume and elimination influence the concentration of drug attained in blood. Consequently, such effects can often be detected and/or prevented by monitoring of serum concentrations of drugs. However, such monitoring alone is insufficient for optimum therapeutic use of drugs and must be accompanied by clinical monitoring of endpoints of efficacy and toxicity, since the relationship between the concentration of drug in serum and response may also be changed. Accumulation of active metabolites that are not measured by conventional drug assays makes interpretation of serum concentrations of drugs such as procainamide particularly hazardous. Effects of renal function on the relationship between amounts of drug in blood and response can only be detected by assessing endpoints of pharmacological effect. Since renal function can affect drug disposition by such a wide variety of mechanisms, the astute clinician must be aware of these potential mechanisms to make best use of his clinical skills and laboratory armamentarium for the benefit of his patients.
肾功能可通过多种方式改变药物剂量与临床疗效之间的关系。对吸收、分布容积和消除的影响会影响血液中达到的药物浓度。因此,通过监测药物的血清浓度,通常可以检测和/或预防此类影响。然而,仅进行此类监测不足以实现药物的最佳治疗应用,还必须伴有对疗效和毒性终点的临床监测,因为血清中药物浓度与反应之间的关系也可能发生变化。常规药物检测无法测定的活性代谢产物的蓄积,使得对普鲁卡因胺等药物的血清浓度进行解释尤其危险。肾功能对血液中药物量与反应之间关系的影响,只能通过评估药理效应终点来检测。由于肾功能可通过多种机制影响药物处置,敏锐的临床医生必须了解这些潜在机制,以便充分利用其临床技能和实验室设备,为患者谋福祉。