Relationship between Urinary Excretion Rate, Steady-State Plasma Levels and Diuretic Response of Furosemide in the Rat

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Abstract
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 µg/ml. Total renal clearance (corrected for kidney function as measured by inulin clearance) showed a negative correlation with plasma concentration (r = –0.655, p < 0.001), and a good correlation was found between urine flow rate and the urinary excretion rate of furosemide (r = 0.777, p < 0.001). Steady-state plasma levels of furosemide showed a poor correlation with urine flow rate (r = 0.377, p > 0.10).