ISSN:
1432-1912
Keywords:
Probenecid
;
Cardiac Glykosides
;
Distribution
;
Mouse
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Distribution studies have been performed on mice with tritium labelled Digitoxin, Digoxin and Ouabain. Contrary to many other species Digitoxin does not lead to an accumulation of radioactivity in the mouse organs. Neither the liver, nor the muscle, nor the kidney concentrations ever reached plasma radioactivity levels; the highest organ concentrations in steady state were found in the liver,and attained between 40 and 50% of plasma radioactivity concentrations. Radiochromatographic controls of these experiments in the liver, bile and plasma showed that Digitoxin is metabolized to a very small extent only and is especially not subject to 12-β-hydroxylation: no Digoxin is demonstrable in liver, bile, plasma, and urine of the mouse following Digitoxin administration. Unlike with Digitoxin is the concentration of Digoxin and Ouabain in the mouse liver very effective. Liver radioactivity after 3H-Digoxin administration is found mostly to be 2–3 fold above plasma level concentrations whereas Ouabain—not metabolized in the mouse—may reach liver concentrations up to 35 times the plasma level. Radioactivity in bile reflects this behaviour: Ouabain bile levels reach the highest values (up to 200 fold) whereas Digitoxin never exceeds plasma radioactivity. When Probenecid was given together with the cardiac glykosides, Digitoxin plasma radioactivity fell to about half of the control values with a slight rise in liver and muscle concentrations. With Digoxin and even more with Ouabain Probenecid inhibited their accumulation in the liver leading to a redistribution into the plasma and muscles with subsequent higher muscle concentrations. The general Probenecid effect was to level out concentration gradients mostly pronounced in the Ouabain experiments where also the effect was achieved with the lowest Probenecid dose (20 mg/kg). A satisfactory explanation for this effet is not yet possible.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00505665
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