The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
SUMMARY We evaluated urinary excretion and tubular transport of 3 H-digoxin by three different methods in anesthetized rats made diuretic by infusion of 2.5% saline. In one group small volumes of 3 H-digoxin and "C-inulin were injected simultaneously into surface proximal convolutions, and urine was collected serially from both ureters. Digoxin recovery was lower after early (62.1 ± 5.3%) than after late (86.9 ± 7.7%) proximal administration but inulin recovery was complete (99.6 ± 2.7%) after all injections. Most of the digoxin was excreted simultaneously with inulin. Delayed recovery was low. In another group of rats digoxin and inulin were applied directly to the capsule of the left kidney. Two-thirds of the recovered digoxin appeared from the left ureter and one-third from the right. The difference (41.9 ± 7.4%) is an estimate of transtubular digoxin influx. Digoxin excretion preceded inulin only on the left. Digoxin to inulin concentration ratios were 6 times higher from the left than the right, whereas inulin recoveries from the two sides were similar. In a third group of rats tubular fluid was collected from surface convolutions of proximal and distal tubule. In the accessible segment of the proximal tubule 35.9% of the filtered digoxin was reabsorbed. In the more distal nephron, drug was added into the lumen; this resulted in a net urinary excretion of 80.2 ± 18.2%. These findings are compatible with free filtration of digoxin at the glomerulus followed by passive proximal tubular reabsorption and an influx against a concentration gradient in the distal nephron.THERAPEUTIC and toxic effects of digoxin depend strongly on its concentration in the blood. Blood levels of digoxin, in turn, are determined by dose and schedule of administration and its physiological disposition. The primary route for elimination of digoxin as the unchanged glycoside is the kidney.1 Its biotransformation and biliary excretion are limited. It has been shown repeatedly that alterations in renal function cause changes in the rate of elimination of digoxin.1 ' 2 The mechanism by which the kidney handles digoxin has'been studied extensively in man and experimental animals. Clearance ratios of digoxin to creatinine were found by several investigators' to be equal, or close to 1. This led to the generally accepted conclusion that digoxin is quantitatively excreted in the urine after filtration in the glomerulus. More recently, Doherty and associates 3 used stop-flow analysis in dogs and observed digoxin to creatinine concentration ratios of less than 1 in the middle segment of the nephron. This finding suggests that there is tubular reabsorption of the drug. Steiness, 4 on the other hand, found digoxin to inulin clearance ratios which were greater than I in man and which suggested an active secretory mechanism that could be inhibited by spironolactone.In our present experiments we used micropuncture tech- Received June 2, 1975; accepted for publication November 13, 1975. niques to examine the renal handling of digoxin in rats with s...
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