Digitoxin Concentrations Research Articles

The binding of 3H-digitoxigenin by guinea-pig atrial tissue.

1. The uptake and release of (3)H-digitoxigenin by electrically driven, guinea-pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations-1 x 10(-7) and 5 x 10(-7) g/ml.-caused a pronounced increase in contractile force.2. The uptake of (3)H-digitoxigenin reached equilibrium after approximately 2 hr of incubation. At equilibrium, the tissue/medium radioactivity ratio reached a value of about 8 for both concentrations studied. After initial saturation of the atria with (3)H-digitoxigenin, approximately 60% of the accumulated genin was released on wash-out in genin-free Tyrode solution for 2 hr.3. After presaturation of the atria with equimolar concentrations of either digitoxigenin or digitoxin (both non-radioactive) the uptake of (3)H-digitoxigenin occurred more slowly. After 2 hr of incubation approximately 60-70% of the tissue bound digitoxigenin or digitoxin had exchanged against (3)H-digitoxigenin from the medium. Presaturation of the atria with ouabain in equimolar concentration did not significantly affect the uptake of (3)H-digitoxigenin.4. The release process of (3)H-digitoxigenin was not affected by the same concentration of non-radioactive digitoxigenin as used for the accumulation of the genin.5. The kinetic properties of (3)H-digitoxigenin, determined by means of isotope techniques, are very similar to those of (3)H-digitoxin. The discrepancy between kinetic and pharmacological behaviour is, however, much larger for digitoxigenin than for digitoxin. Obviously, the presence or absence of the sugar moieties considerably influences the behaviour of the molecule towards the specific receptors, without particularly affecting the binding to unspecific, cellular structures.

強心配糖体の代謝と分布に関する研究 (第3報)

The extent of binding of digitoxin and its metabolites to bovine albumin or rat serum was determined by the method of equilibrium dialysis or ultrafiltration. The results were as follows:1) It was found that the binding effect of bovine albumin or rat serum was most marked with digitoxigenin monodigitoxoside, less with digitoxin and digitoxigenin didigitoxoside, and least with digoxin.2) With increasing concentration of digitoxin, digitoxigenin didigitoxoside or didigitoxigenin monodigitoxoside the binding proportion decreased.3) In a phosphate buffer of pH 6.4-9.2, there was no obvious effect of pH on the drug-protein binding.

The deposition of digitoxin in the tissues of the rat after parenteral injection.

Quantitative studies regarding the fate of parenterally injected digitoxin in the rat were made by assaying extracts of rat tissue by the embryonic duck heart method. The concentration of digitoxin found in heart muscle was similar to that found in lung and kidney and greater than the concentration in skeletal muscle. The greatest amount was found in the liver and suggested the importance of this organ in the excretion or destruction of digitoxin.

Quantitative Detection of Minute Concentrations of Digitoxin.

Conclusions1. Quantitative assay of extremely minute amounts of digitoxin in Tyrode's solution and in rat and human serum was found to be possible by means of the embryonic duck heart preparation.

Colorimetric assay of digitoxin

A colorimetric method in which sodium beta-naphthoquinone-4-sulfonate (purified) is reacted with digitoxin in alkaline solution to form a purple color is proposed for the determination of digitoxin. The purple color quickly reaches a maximum and fades, but the addition of acetic acid at the time of maximum development changes the color to yellow and stabilizes it. The procedure involves no special equipment and may be adapted to any colorimeter or spectrophotometer by appropriate changes in the digitoxin concentration to suit the particular instrument. Data and tables are given to show results obtained with various samples of digitoxin and with several lots of tablets.

Studies on purified digitalis glucosides. III. The relationship between therapeutic and toxic potency: Cattell, M., and Gold, H.: J. Pharmacol. & Exper. Therap. 71: 114, 1941

The relative potency with regard to both therapeutic and toxic effects on isolated papillary muscles from the cat have been determined for the following glucosides: Ouabain (Merck), Digitoxin (Merck), (Laboratoire Nativelle), Lanatoside A (Sandoz), Lanatoside B (Sandoz) and Lanatoside C (Cedilanid, Sandoz). The minimum concentration of ouabain and digitoxin, i.e., that causing increased force of contraction in 50 per cent of experiments (therapeutic effect) is 1 part in 100 millions of Locke's solution; for the lanatoside compounds it is approximately 1 part in 10 millions. When the concentration of any of the glucosides is sufficiently increased toxic effects are produced, including extra contractions, loss of excitability and diminished force of contraction. The ratio of the concentrations producing therapeutic and toxic effects is the same for Digitaline Nativelle and ouabain. There is also similarity among the several lanatoside glucosides studied, and thus by this technic we have not been able to confirm the wide margin between the therapeutic and toxic dose reported by Moe and Visscher for lanatoside C. Ouabain and Digitaline Nativelle both give a slightly higher value for the ratio of toxic to therapeutic concentration in comparison with the lanatoside compounds. The evaluation of the significance of this finding must await further evidence. The available evidence pertaining to the questions of differences in the relationship between toxic and therapeutic doses among different glucosides is discussed, and the conclusion is reached that proof of the existence of such differences is still wanting.