Absence of a clinically significant interaction between theophylline and furosemide

In new of previous contradictory results, the possible interaction between the loop diuretic furosemide and theophylline was re-evaluated in 12 healthy volunteers with a steady-state plasma theophylline level. Two doses of furosemide 20 mg at a 4 h interval did not influence the steady-state plasma concentration of theophylline despite causing a moderate diuresis. Urinary recovery of theophylline and its metabolites amounted to 106 +/- 21% of the dose without furosemide and 96 +/- 19% of the dose with furosemide, demonstrating that there was no influence on the enteral absorption of theophylline of the furosemide treatment. After the first dose of furosemide the fractional renal clearance (CLR1) of theophylline (fractional = hourly sampling period) changed in parallel with the urinary flow rate, without a significant difference between treatment with and without furosemide. After the second dose of furosemide, CLR1 was increased in the first hour and then it declined to levels far lower than the control value. This unexpected result could explain the unchanged plasma concentration of theophylline during furosemide treatment.