[The past and the present of cardiac glycosides. III. Pharmacokinetics]. / Minulost a soucasnost srdecních glykozidu. III. Farmakokinetika.

The molecular structure is one of the keypoints that govern both the extent of extracardiac action of cardiac glycosides and their different kinetics. The apolar, fat soluble digitoxin is very well absorbed from the intestine, its onset of action is slow, binds to a high degree to albumin and undergoes enterohepatic recirculation which accounts for a long elimination half time and stability of plasmatic levels. Digitoxin is largely excreted via gastrointestinal tract. The absorption of digoxin is less reliable, onset of action occurs earlier and the binding to albumin is considerably less than that of digitoxin. The drawback, however small, of digoxin lies in a lower stability of plasma levels and prevailing renal excretion. The molecule of strophatin is highly polar, its absorption from the intestine negligible and can be administered only intravenously. The onset of action is prompt, elimination half time short and about half the injected amount is excreted extrarenally.

[Chronopharmacodynamics of delayed-action cardiac glycosides and nitrates]. / Khronofarmakodinamika serdechnykh glikozidov i nitratov prolongi- rovannogo deistviia.

In 96 patients with coronary heart disease and stage II circulatory failure, the chronopharmacodynamics of strophanthin, corglycon, and nitrosorbide was studied by using acute clinical and pharmacological tests in the morning (8.00 a.m.), in the afternoon (2.00 p.m.), and in the evening (8.00 p.m.). Central and peripheral hemodynamic parameters were measured prior to and following 5, 15, 30, 60, and 120 min of intravenous injection of cardiac glycosides or sublingual administration of nitrosorbide in a dose of 10 mg for 240 min. The investigations showed that there were the most profound hemodynamic changes in the morning if strophanthin was used and in the afternoon if corglycon was given. The maximal reduction in heart pre- and afterload was seen in the morning when nitrosorbide was applied, the most improvement in central hemodynamic parameters was observed in the evening when nitrosorbide was used.

Biodistribution of two 99mTc-cardiac glycosides with end glucose unit: effect of lipophilicity on their relative myocardial accumulation.

In biodistribution experiments with tritium labelled cardiac glycoside it was observed that compounds of low lipophilicity showed a considerably higher affinity towards myocardium with respect to other tissues and organs. A similar trend was also observed with 99mTc-cardiac glycosides except for one compound with glucose residue, which in spite of its lower lipophilicity exhibited an unexpectedly low heart to non-target concentration ratio, thereby indicating a possible influence of carbohydrate residue on biodistribution. To confirm this, in this article we radiolabelled two glucose containing cardiac glycosides (K-strophanthin-beta and K-strophanthoside) with 99mTc and, in biodistribution experiments, less lipophilic 99mTc-K-strophanthoside showed a much better heart to non-target ratio over 99mTc-K-strophanthin-beta. It is thus concluded that, in addition to lipophilicity, the affinity of the carbohydrate residue for non-target organs is also an important consideration in determining the structure-distribution relationship of 99mTc-cardiac glycosides.

Preparation and evaluation of technetium-99m labeled cardiac glycoside derivatives as potential myocardial imaging agent.

Three cardiac glycosides, two natural, cymarin and convallotoxin and one synthetic, strophanthidin-beta-D-glucoside were converted to their thiosemicarbazone and subsequently radiolabeled with 99mTc by chelation. The resulting radioactive chelate complexes were evaluated in animals to determine the suitability of this class of compounds for myocardial imaging. It was observed from the animal biodistribution data of the three radioactive compounds, there was a considerable variation in the heart to non-target organ uptake ratio. A possible explanation of this variation was offered in the light of their lipophilic character, protein binding ability and affinity towards non-target receptors. It is anticipated that this study may help to develop a 99mTc-cardiac glycoside complex with better distribution characteristics, and such a compound may offer a suitable alternative to 201Tl, which is at present used for myocardial imaging.