Diuretic bioactivity optimization of furosemide in rats.

Furosemide is a loop diuretic widely used by patients with congestive heart failure (CHF) to rid excess body water, reducing blood pressure, and mobilizing edemas. However, due to the narrow window of furosemide absorption, occurring only in the proximal gastrointestinal tract, only immediate release oral formulations are clinically available. Comparisons of bolus and continuous administration of furosemide in intravenous settings demonstrate that continuous administration at lower concentrations produced greater diuretic efficiency and reduced subsequent hospitalization rates in patients experiencing severe CHF. We report a systematic investigation of the diuretic bioactivity profiles of phase inversion micronized furosemide and furosemide co-precipitated with Eudragit L100, as well as their blends with stock furosemide, targeted at reducing the rapid spike in diuresis associated with immediate release formulations while maintaining cumulative urine output. Of the formulations tested, an equal parts blend of micronized furosemide and stock furosemide demonstrated optimal diuretic bioactivity profiles in a rat model.