Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly.

In a cross-sectional study of the pharmacokinetics and pharmacodynamics of peroral and intravenous bumetanide (0.5 mg, single dose), total and renal clearance of the diuretic was significantly lower in elderly persons than in young adults, resulting in higher bumetanide plasma levels in the aged. Nonrenal clearance, bioavailability, and the volume of distribution were not significantly changed. Together with the decreased delivery into the urine the diuretic and natriuretic effect of bumetanide was reduced in the elderly. Renal clearance of bumetanide was linearly related with creatinine clearance, hence the decreases in bumetanide clearance and diuretic efficacy in the elderly are attributed to the age-dependent decline in renal function. The bumetanide concentration in urine and the fractional sodium excretion were not different in the two age groups, suggesting that the decrease in diuretic response in the elderly is a result of a reduction in the number of functioning nephrons, whereas the response of the remaining nephrons to bumetanide is unaltered.