Furosemide kinetics and dynamics in aged patients

Furosemide (F) is frequently used by elderly persons. We wanted to know whether age-related changes in the disposition or the effect of F occurred and whether these changes could be predicted or explained. Kinetics and diuretic effects were studied after intravenous F injection in geriatric patients (70 to 93 yr of age). The changes in kinetics were as follows: slightly enlarged volume of distribution (0.16 +/- 0.04 l) inversely related to serum albumin, diminished total body clearance (73 +/- 27 ml/min), decreased renal clearance (40 +/- 18 ml/min), and prolonged elimination t1/2 (180 +/- 87 min). F effects were unchanged only if the decreased renal delivery of F and the decreased glomerular filtration rate were taken into account. Renal F clearance correlated best with endogenous creatinine clearance (ECC) and with F effects. Only ECC and plasma creatinine turned out to be useful patient characteristics to predict all F effects. Many drugs have an increased effect in elderly persons if a standard dose is used, based on the attainment of higher free plasma levels. In the case of F, however, the effects are decreased because they depend on decreased glomerular filtration of electrolytes and water and on decreased renal F secretion. These decreases are in part age dependent and in part disease dependent.