ISOSORBIDE: EFFECTS ON RENAL FUNCTION, RENAL CLEARANCE AND TUBULAR HANDLING AND VOLUME OF DISTRIBUTION IN DOGS

¹ Department of Metabolism, Division of Medicine, Walter Reed Army Institute of Research, Washington, D.C.

Isosorbide was noted in previous studies to produce diuresis after p.o. administration to rats. In the present studies with classical clearance methods, isosorbide administered p.o. was found to produce a consistent osmotic diuresis and saluresis after doses of 1.0 and 2.0 g/kg b.wt. in unanesthetized dogs. Glomerular filtration rate and effective renal plasma flow were not altered. The renal clearance of C¹⁴-isosorbide was found to be 80% of infulin and creatinine clearance, approximately equal to urea clearance and related to urinary flow rate. Isosorbide administered i.v. produced less solute excretion than an equimolar dose of mannitol. The space of distribution of C¹⁴-isosorbide was found to be 54% b.wt. in intact and nephrectomized dogs. Stop-flow studies demonstrated proximal tubular reabsorption of the compound, believed to be passive in nature for several reasons.