Bumetanide kinetics in renal failure

Journal Article · Wed May 01 00:00:00 EDT 1985 · Clin. Pharmacol. Ther.; (United States)

DOI:https://doi.org/10.1038/clpt.1985.91· OSTI ID:5324152

Pentikaeinen, P J.P.; Pasternack, A; Lampainen, E; Neuvonen, P J; Penttilae, A

To study the effects of renal failure on bumetanide kinetics, the authors administered single intravenous doses of 1.0 mg/3.08 microCi /sup 14/C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of /sup 14/C-bumetanide and total /sup 14/C 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 +/- /sup 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 /sup 14/C 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.

• Research Organization: Univ. of Helsinki, Finland
• OSTI ID: 5324152
• Journal Information: Clin. Pharmacol. Ther.; (United States), Journal Name: Clin. Pharmacol. Ther.; (United States) Vol. 5; ISSN CLPTA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
BENZOIC ACID
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BLOOD-PLASMA CLEARANCE
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CLEARANCE
EXCRETION
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
LABELLED COMPOUNDS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATIENTS
PROTEINS
REACTION KINETICS
RENAL CLEARANCE
TRACER TECHNIQUES