Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies on the pharmacokinetics of 3H-digoxin in the rat have been based on total radioactivity in the plasma, even though the drug is extensively metabolized in this species. A comparison of total radioactivity vs. unchanged drug in rat plasma after administration of 3H-digoxin clearly showed the need to separate digoxin from its metabolites. The pharmacokinetics of digoxin were therefore examined using solvent extraction and thin-layer chromatography to isolate unchanged drug. Digoxin levels after a 1 mg/kg iv dose were measured in the plasma and urine of adult male rats in which the bile duct or the ureters had been ligated, as well as in sham-operated controls. In all cases, digoxin concentrations were best described by a two-compartment open model. Digoxin was rapidly eliminated from the plasma of controls, with a half-life of 2.5 hr, a volume of distribution of 3.6 liter/kg, and a renal clearance somewhat lower than the glomerular filtration rate. No significant change in these parameters was observed in rats with bile duct ligation. The total body clearance of 5.77 ml/min in the controls was reduced by only 10% in the bile duct-ligated rats. In animals with bilateral ureter ligation, the body clearance was reduced by 30% and the plasma half-life of digoxin was increased to 4 hr, although no significant change in the apparent volume of distribution was noted. Approximately 60% of the total body clearance was unaffected by bile duct and ureter ligations, and was assumed to be due to biotransformation. Biliary excretion was found to be important for digoxigenin bisdigitoxoside, inasmuch as rats with bile duct ligation showed elevated metabolite levels in the plasma as well as a 3-fold increase in renal excretion of the bisglycoside.
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PMID:Pharmacokinetics of digoxin in the rat. 0 7

We evaluated urinary excretion and tubular transport of 3H-digoxin by three different methods in anesthetized rats made diuretic by infusion of 2.5% saline. In one group small volumes of 3H-digoxin and 14C-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.
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PMID:Renal tubular transport of 3H-digoxin in saline diuresis in rats. 124 66

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 reabsorption of water and efflux 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 form 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 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.
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PMID:Digoxin transport in the distal nephron of rats during saline diuresis. 732 67