title: Natriuretic efficiency of frusemide as a consequence of drug input rate.
abstract: OBJECTIVE
  The aim of the present study was to investigate the influence of the rate of delivery of frusemide to its site of action on the effect and efficiency of the drug.
  
  
  METHODS
  Frusemide 30 mg was administered as a bolus dose, a slow-rate infusion and a bolus dose in combination with 2 g of probenecid in a three way cross-over design to seven healthy volunteers. Urinary volume and contents of frusemide and sodium were measured in samples collected over 10 h.
  
  
  RESULTS
  Total natriuretic response was 40% higher (P < 0.001) after the infusion and 20% higher (P < 0.05) after the combined treatment with probenecid, as compared with the bolus dose. Total natriuretic efficiency did not differ between the infusion (0.013 mmol microg(-1)) and the combined treatment with probenecid (0.015 mmol microg(-1)), but was significantly higher as compared with the bolus dose (0.009 mmol microg(-1)). Natriuretic effect data were modeled according to the sigmoid Emax model and the frusemide excretion rate with maximum efficiency (ER(effmax)) was calculated from the estimated parameters. For both the frusemide infusion and the combined treatment with probenecid, the time course of delivery of frusemide into the urine consistently approached ER(effmax) more closely than was the case for the bolus dose. The natriuretic effect vs frusemide excretion rate curves were shifted to the right, and the estimated values of the sigmoid Emax model were higher for EC50 and lower for the slope factor after the bolus dose, which may indicate tolerance development for this treatment.
  
  
  CONCLUSIONS
  Slowing the delivery of frusemide to the site of action increased the efficiency of the drug, leading to an increased natriuretic response.
authors.affiliation: Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wakelkamp
authors.forename: G
authors.initials: G
authors.lastname: Alván
authors.forename: G
authors.initials: G
authors.lastname: Paintaud
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects*
chemical_list: D004232:Diuretics; D005665:Furosemide