[Pharmacokinetic and cardiac efficacy of beta-acetyldigoxin and digitoxin in combination therapy with 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)
D000113:Acetyldigoxins / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure; D004074:Digitoxin / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D004077:Digoxin / Q000031:analogs & derivatives*; D004110:Diltiazem / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011674:Pulse
D000113:Acetyldigoxins; D001552:Benzazepines; D004077:Digoxin; D004074:Digitoxin; D004110:Diltiazem
Pharmakokinetik und kardiale Wirksamkeit von beta-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Diltiazem.