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), Vol. 5
• Country of Publication: United States
• Language: English

Related Subjects

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