Unit of Geriatric Pharmacoepidemiology, Italian National Research Center on Aging (INRCA), C.da Muoio Piccolo, I-87100, Cosenza, Italy.
Drug Saf. 2012 Jan;35 Suppl 1:47-54. doi: 10.1007/BF03319102.
The aging process is characterized by relevant changes in pharmacokinetics. Renal function is known to decline with aging. However, as a result of reduced muscle mass, older individuals frequently have a depressed glomerular filtration rate (GFR) despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly on the clearance of hydrosoluble drugs, as well as the risk of adverse drug reactions (ADRs) from hydrosoluble drugs. The assessment of renal function should thus be a mandatory item in the global examination of patient characteristics. Equations for estimating GFR have become very popular in recent years. However, different equations may yield significantly different estimated glomerular filtration rate (eGFR) values, which have important implications in dosing drugs cleared by the kidney. Current knowledge suggests that eGFR based on the Chronic Kidney Disease-Epidemiological Collaboration (CKD-EPI) study equation outperformed eGFR based on the Modification of Diet in Renal Disease (MDRD) study equation and creatinine clearance estimate based on the Cockcroft-Gault formula as a predictor of ADRs from kidney cleared drugs. More recently, the combined creatinine-cystatin C equation was shown to perform better than equations based on either of these markers alone in diagnosing CKD, even in older patients. However, its accuracy in predicting ADRs and usefulness in drug dosing is still to be investigated.
衰老是一个以药代动力学相关变化为特征的过程。众所周知,肾功能会随着年龄的增长而下降。然而,由于肌肉量减少,老年人的肾小球滤过率(GFR)即使在血清肌酐正常的情况下也常常降低,而这种隐匿性的肾功能不全可能会显著影响水溶性药物的清除率,以及水溶性药物不良反应(ADR)的风险。因此,肾功能评估应该成为患者特征全面检查的强制性项目。估算 GFR 的方程在近年来变得非常流行。然而,不同的方程可能会产生显著不同的估算肾小球滤过率(eGFR)值,这对通过肾脏清除的药物的剂量具有重要意义。目前的知识表明,基于慢性肾脏病-流行病学合作(CKD-EPI)研究方程的 eGFR 优于基于肾脏病饮食改良(MDRD)研究方程和 Cockcroft-Gault 公式的估计肌酐清除率作为预测肾脏清除药物 ADR 的指标。最近,研究表明,联合肌酐-胱抑素 C 方程在诊断 CKD 方面的表现优于仅基于这些标志物之一的方程,甚至在老年患者中也是如此。然而,其预测 ADR 的准确性和在药物剂量方面的实用性仍有待研究。