Bumetanide kinetics in renal failure.
To study the effects of renal failure on bumetanide kinetics, we administered single intravenous doses of 1.0 mg/3.08 microCi 14C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of 14C-bumetanide and total 14C were adequately described by a two-compartment open model in the control subjects and in the patients. The volume of the central compartment and the distribution t1/2 were of the same order in both groups, whereas the mean (+/- SE) volume at steady state was larger (22.1 +/- 1.6 and 16.9 +/- 1.0 L) and the elimination t1/2 was longer (1.9 +/- 0.2 and 1.4 +/- 0.1 hours) in patients with renal failure than in healthy controls. Bumetanide renal clearance was lower (10 +/- 3 and 90 +/- 13 ml/min) in patients than in subjects and correlated with creatinine clearance (r = 0.784) and log serum creatinine level (r = -0.843), whereas nonrenal clearance was significantly higher in the patients (153 +/- 14 and 99 +/- 6 ml/min). Bumetanide total plasma clearance did not significantly change. The non-protein-bound, free fraction of bumetanide was higher in patients and correlated with plasma albumin levels (r = -0.777). The kinetics of total 14C showed similar but greater changes than those of 14C-bumetanide. Thus the most important changes in bumetanide kinetics in patients with renal failure are low renal clearance and a high free fraction, with a consequent increase in nonrenal clearance, volume of distribution, and elimination t1/2.
D058186:Acute Kidney Injury / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002034:Bumetanide / Q000097:blood / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004232:Diuretics / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D002250:Carbon Radioisotopes; D004232:Diuretics; D002034:Bumetanide