Effect of food on the absorption of frusemide and bumetanide in man.

1. The influence of food on the absorption of frusemide and bumetanide was compared in two separate randomized crossover studies. 2. On three separate occasions frusemide 40 mg was administered to eight healthy male volunteers intravenously, orally in the fasting state and orally after a standard breakfast. Blood and urine were collected at intervals over 8 h and urine alone for a further 16 h. The study was then repeated in nine healthy volunteers using intravenous and oral bumetanide 2 mg. 3. Breakfast significantly reduced the peak plasma concentration of frusemide from 2.35 +/- 0.49 to 0.51 +/- 0.19 mg l-1 (95% confidence intervals (95% CI) = 1.39 to 2.28 mg l-1) and delayed the time to peak concentration from 0.69 +/- 0.21 to 1.91 +/- 0.93 h (95% CI = 0.41 to 2.03 h). The oral bioavailability of frusemide was significantly reduced by approximately 30% (75.6 +/- 10.6 to 43.2 +/- 16.8%; 95% CI = 13.5 to 51.4%). 4. With bumetanide, the meal also significantly reduced the peak concentration from 0.097 +/- 0.015 to 0.036 +/- 0.012 mg l-1 (95% CI = 0.048 to 0.073 mg l-1) and delayed the time to peak from 0.53 +/- 0.08 to 1.36 +/- 0.72 h (95% CI = 0.23 to 1.44 h). However, food had no statistically significant effect on the bioavailability and urinary recovery of bumetanide. 5. In this study, the absorption of bumetanide was affected less than frusemide by food.