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Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with congestive heart failure.

Abstract
Four healthy subjects and six patients with congestive heart failure (CHF) were given 3 mg oral and intravenous doses of bumetanide in a random crossover fashion. Bumetanide was analyzed by HPLC, and sodium and potassium was analyzed by flame photometry. Aside from a modest reduction in renal clearance, the kinetics of bumetanide in CHF were similar to those in healthy subjects. The extent of bioavailability was 81%, with a variability of 20% to 25% about the mean for both groups. The cumulative dynamic responses to bumetanide, whether administered orally or intravenously, were essentially the same in each group. Pharmacodynamic modeling showed that there were no significant differences between healthy subjects and patients with CHF in either ER50 (bumetanide urinary excretion rate producing 50% of maximum drug effect) or S (slope), although the baseline effect was 15 times lower in CHF. The maximum effect attributable to bumetanide was twofold higher in healthy subjects and there was a significant correlation between this parameter and creatinine clearance (r = 0.964; p less than 0.001). Overall, these results indicate that a predictable transition from 3 mg intravenous to oral doses of bumetanide is possible in CHF.
AuthorsJ A Cook, D E Smith, L A Cornish, R M Tankanow, J M Nicklas, M L Hyneck
JournalClinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 44 Issue 5 Pg. 487-500 (Nov 1988) ISSN: 0009-9236 [Print] UNITED STATES
PMID3180632 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Blood Proteins
  • Diuretics
  • Bumetanide
Topics
  • Administration, Oral
  • Adult
  • Aged
  • Biological Availability
  • Blood Proteins (metabolism)
  • Bumetanide (administration & dosage, pharmacokinetics)
  • Diuretics (pharmacokinetics)
  • Dose-Response Relationship, Drug
  • Female
  • Heart Failure (drug therapy, metabolism)
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Random Allocation

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