title: Relationship between urinary excretion rate, steady-state plasma levels and diuretic response of furosemide in the rat.
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 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).
mesh_terms: D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D005665:Furosemide / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007444:Inulin; D008297:Male; D051381:Rats; D013997:Time Factors
chemical_list: D005665:Furosemide; D007444:Inulin