Relationship between urinary excretion rate, steady-state plasma levels and diuretic response of furosemide in the rat

The purpose of the present study was to determine if furosemide's active transport process could be saturated at therapeutic concentrations and to define a relationship between furosemide in a measurable sampling compartment and its diuretic effect. The experiments utilized Sprague-Dawley rats, ranging in weight from 248 to 313 g, anesthetized with sodium pentobarbital (60 mg/kg). The femoral artery and vein as well as the bladder were cannulated, and samples were taken to measure inulin and furosemide concentrations. 28 rats were infused, after a suitable loading dose (0.5--1.5 mg/kg), to steady-state plasma furosemide levels over the therapeutic concentration range 0.8--25.1 micrograms/ml. Total renal clearance (corrected for kidney function as measured by inulin clearance) showed a negative correlation with plasma concentration (r = -0.655 p less than 0.001), and a good correlation was found between urine flow rate and the urinary excretion rate of furosemide (r = 0.777, p less than 0.001). Steady-state plasma levels of furosemide showed a poor correlation with urine flow rate (r = 0.377, p greater than 0.10).