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Natriuretic efficiency of frusemide as a consequence of drug input rate
Author(s) -
Wakelkamp Monique,
Alván Gunnar,
Paintaud Gilles
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00592.x
Subject(s) - probenecid , natriuresis , bolus (digestion) , diuretic , chemistry , furosemide , excretion , pharmacology , medicine , endocrinology
Aims 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 μg −1 ) and the combined treatment with probenecid (0.015 mmol μg −1 ), but was significantly higher as compared with the bolus dose (0.009 mmol μg −1 ). Natriuretic effect data were modeled according to the sigmoid E max 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 E max model were higher for EC 50 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.