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Digoxin Transport in the Distal Nephron of Rats during Saline Diuresis

Abstract The nephron segments involved in the renal tubular transport of digoxin and the direction of transport in each segment were evaluated using renal micropuncture techniques in 11 rats made diuretic by i.v. infusion of .85% saline. Tubular fluid was collected from 4 different sites along the nephron: late proximal, early distal, late distal, and ureter. The concentrations of 3H-digoxin and 14C-inulin were measured in each sample and the reab-sorption of water and efflux or influx of digoxin were calculated. Water was removed from the lumen along the entire length of the nephron and only 2.53 ± 0.3% of the filtrate was excreted in the urine. Digoxin was also absorbed in the proximal convoluted tubule and in the loop of Henle. About 1/3 of the filtered drug exited in these early nephron segments probably by passive diffusion. In the distal convoluted tubule, digoxin was added to the tubular fluid. The fraction of digoxin present in the lumen increased from 64 ± 3.8% of the filtered load at early distal site to 78.7% ± 4.8% at late distal site indicating that an amount equal to 15% of filtered digoxin entered the tubule. This influx occurred against a concentration gradient of 3-5, suggesting the existence of a carrier mediated or active transport mechanism in this nephron segment. Transport of digoxin beyond the late distal puncture site was negligible. The collecting duct appeared to be relatively impermeable to the drug since a concentration gradient of 30 or greater failed to cause its diffusion out of the tubule. The data indicate bidirectional transport of digoxin in the rat nephron. Efflux occurs primarily in the early nephron segments while net influx is limited to the distal convoluted tubule.