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Controversy persists regarding the role of tubular reabsorption and secretion in the renal handling of digoxin. To determine the effect of reduction in renal perfusion pressure and blood flow on digoxin clearance during acute and chronic digoxin administration, renal clearances of digoxin and inulin were measured in pentobarbital–anesthetized dogs before and after repeated unilateral renal artery constriction. After reduction of renal arterial mean pressure to 67% of the control level, both inulin and digoxin clearances fell sharply, by 62–86% (p < 0.001). The digoxin–to–inulin clearance ratio in the arterially constricted kidney decreased only slightly, from 0.82 to 0.76 (p < 0.02) after unilateral renal artery constriction in the chronically digitalized group as determined by 3H counts in serum and urine of dogs given 12 α-[3HJ digoxin. No significant change in the digoxin–to–inulin clearance ratio after renal arterial constriction was found by radioimmunoassay determination of digoxin in chronically dosed dogs. Digoxin–to–inulin clearance ratio also did not change significantly with renal artery constriction in the acutely digitalized group (0.72 vs 0.71). Slightly higher digoxin–to–inulin clearance ratios in chronically (mean 0.82) compared with acutely (mean 0.73; p = 0.038) digitalized dogs may be accounted for by renal parenchymal digoxin binding under non–steady–state conditions of acute digoxin administration. These data support the concept that glomerular filtration is the principal mechanism of renal digoxin excretion. Reduction in renal arterial pressure, with consequent decrease in glomerular filtration and urine flow, produces a marked fall in digoxin clearance but no appreciable change in the digoxin–to–inulin clearance ratio in dogs given digoxin acutely or dosed chronically to attain a steady state. This is consistent with the absence of any important change in net tubular reabsorption of digoxin under these experimental circumstances. These experiments show that renal excretion of digoxin in the dog closely approximates the filtered load over a broad range of renal arterial perfusion pressures and urine flow rates.

The effect of altered renal perfusion pressure on clearance of digoxin.