[Pharmacokinetic and cardiac efficacy of beta-acetyldigoxin and digitoxin in combination therapy with diltiazem]. / Pharmakokinetik und kardiale Wirksamkeit von beta-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Diltiazem.

The effect of diltiazem (D) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 12) and digitoxin (DGT; n = 10) was studied in 22 patients with cardiac insufficiency stages II-III by the New York Heart Association. Glycoside plasma concentration and renal excretion as well as electrocardiogram [heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T-waves in leads V2 to V6 (TV2-6)] and systole time intervals [total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET ratio] were recorded repeatedly before and during co-administration of 180 mg/day D. In eight patients digoxin plasma levels increased continuously during additional D administration. After reaching a new steady state at 0.93 +/- 0.35 ng/ml digoxin concentrations were at an average 43% higher than before D administration (0.65 +/- 0.27 ng/ml) with a simultaneous increase in renal glycoside excretion. The other four patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only half the patients treated with DGT and D revealed an increase in DGT plasma levels of 21.4%. Daily renal glycoside excretion was not altered by D administration. In accordance to the increasing AD plasma concentration, PQ-interval was prolonged and T-wave flattening was intensified, whereas the systolic time intervals after concomitant treatment of AD and D did not differ from those after AD alone.(ABSTRACT TRUNCATED AT 250 WORDS)

[Renal and extracorporeal elimination of digoxin and its methylated and acetylated derivatives]. / Untersuchungen zur renalen und extrakorporalen Elimination von Digoxin und seinen methylierten und azetylierten Derivaten.

This study was performed to get more informations on the renal and extracorporeal elimination of digoxin. The first part of this study demonstrated that a radioimmunoassay for digoxin or a specific tritium label of digoxin is necessary to measure renal digoxin clearances. Randomly labeled 3H-digoxin may loose its label and thus give incoherent results. A comparison of digoxin and inulin clearances in patients demonstrates glomerular filtration as the major renal excretion pathway of digoxin, but a major fraction of the glycoside is excreted by tubular secretion. Opposite to digoxin, beta-methyl-digoxin undergoes less tubular secretion but eventually additional tubular reabsorption. The insertion of digoxin and quinidine may be a further prove for the existence of a tubular secretion of digoxin. While the renal clearance of digoxin is significantly bigger than the renal clearance of creatinine, additional quinidine therapy reduces the renal clearance of digoxin to the one of creatinine. We studied the renal excretion mechanism of digoxin additionally in an animal model of acute prerenal failure. After a 33% reduction of renal arterial pressure glomerular filtrate dropped 68%. Under these circumstances the renal excretion mechanism of digoxin measured as the digoxin to inulin clearance ratio did not change. We evaluated the efficiency of hemodialysis, hemofiltration and hemoperfusion to eliminate digoxin. Although digoxin is eliminated by all three methods, even the most effective, hemoperfusion, can reduce total body content of digoxin less than 3%. Thus we conclude that all these methods have no indication in the treatment of digoxin intoxications.