The pharmacokinetics of frusemide are influenced by age.

Abstract

After a 24 h control period 80 mg frusemide was given intravenously over 2 min to a group of young and a group of elderly healthy male volunteers. The serum concentration of frusemide and the excretion in urine of the drug and a glucuronidated metabolite were followed for 24 h. The elimination of the drug from serum was described by an open two compartment model. The serum clearance (CLs) was 170 +/‐ 19 ml min‐1 in the young and 129 +/‐ 11 ml min‐1 in the elderly (P less than 0.01) and the average renal clearance (CLr) was 67% of CLs in the young and 58% of CLs in the elderly (NS). The average amount of unchanged frusemide in the urine during the first 30 min was 30 +/‐ 6 mg in the young but only 20 +/‐ 4 mg in the elderly (P less than 0.01). The albumin concentration in serum was 15% lower in the elderly but on the average the protein bound fraction of frusemide was 98.6% in both groups. The Vd ss did not differ between the two age groups (0.130 1 kg‐1) but the elimination half‐life was 70 +/‐ 20 min in the young and 102 +/‐ 33 min in the elderly (P less than 0.05). In the young 11.4 +/‐ 5.0 mg frusemide was excreted as a glucuronidated compound whereas this figure was only 5.4 +/‐ 2.9 mg in the elderly (P less than 0.01). It is concluded that the age‐related changes in the fate of unchanged frusemide in the organism mainly can be explained by a reduction in the tubular secretion of the drug which in turn may be caused by a reduction in renal plasma flow. 1983 The British Pharmacological Society