[Pharmacokinetics and cardiac effect of beta-acetyldigoxin and digitoxin in combination therapy with nifedipine].
The effect of nifedipine (N) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 11) and digitoxin (DGT; n = 10) was studied in 21 patients with cardiac insufficiency stage II-III NYHA. 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 systolic 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-administrations of 40-60 mg/day N. Plasma AD concentrations were 0.64 +/- 0.22 ng/ml (mean +/- SD) before and 0.61 +/- 0.21 ng/ml during co-administration of N over 10-14 days, plasma DGT concentrations 13.9 +/- 4.1 ng/ml before and 13.7 +/- 4.5 ng/ml during co-administration of N over 4-6 weeks. Daily glycoside excretion was not affected by treatment with N. Heart rate and PQ-interval were not significantly changed during co-administration of N whereas T-wave flattening was intensified and QT-duration was lengthened. Concomitant treatment of AD and N led to an increase of PEPI and PEP/LVET compared to AD alone in ten patients whereas the systolic time intervals after concomitant treatment of DGT and N in most patients did not differ from those after DGT alone. From our findings we conclude that N had no clinically significant effect on pharmacokinetics and pharmacodynamics of AD or DGT.
D000112:Acetyldigitoxins / Q000378:metabolism / Q000627:therapeutic use*; D000368:Aged; D004074:Digitoxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*
D000112:Acetyldigitoxins; D004074:Digitoxin; D009543:Nifedipine
Pharmakokinetik und kardiale Wirksamkeit von beta-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Nifedipin.