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Effects of diltiazem on pharmacokinetics and pharmacodynamics of beta acetyldigoxin and digitoxin in patients

, : Effects of diltiazem on pharmacokinetics and pharmacodynamics of beta acetyldigoxin and digitoxin in patients. Klinische Wochenschrift 63(14): 636-642

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 8 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 4 patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only 1/2 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. In contrast, the lesser increase of DGT plasma concentration seems not to be cardiac active as shown by the different electrocardiogram parameters and systolic time intervals. AD plasma concentration apparently should be controlled in patients receiving a combined therapy of AD and D until the new steady-state concentrations are obtained and the AD dose reduced if there is evidence of toxicity. On the other hand, such measurement seems unnecessary during combination of DGT and D.


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