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[Pharmacokinetics and cardiac effect of beta-acetyldigoxin and digitoxin in combination therapy with nifedipine]
Abstract:
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.
Insights
Nifedipine (N) showed no significant impact on the pharmacokinetics or pharmacodynamics of beta-acetyldigoxin (AD) or digitoxin (DGT) in patients with cardiac insufficiency. This suggests nifedipine can be safely co-administered with these cardiac glycosides.
Area of Science:
- Cardiology
- Clinical Pharmacology
- Pharmacokinetics and Pharmacodynamics
Background:
- Cardiac glycosides like beta-acetyldigoxin (AD) and digitoxin (DGT) are crucial in managing cardiac insufficiency.
- Nifedipine (N), a calcium channel blocker, is frequently prescribed, raising questions about potential drug interactions.
Purpose of the Study:
- To investigate the effects of nifedipine on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin and digitoxin in patients with cardiac insufficiency.
- To assess the clinical significance of potential interactions between nifedipine and these cardiac glycosides.
Main Methods:
- A study involving 21 patients with cardiac insufficiency (NYHA stage II-III) who received either beta-acetyldigoxin or digitoxin.
- Measurements included glycoside plasma concentrations, renal excretion, heart rate, ECG parameters (PQ, QTc), and systolic time intervals before and during nifedipine co-administration.
- Pharmacokinetic parameters (plasma concentration, excretion) and pharmacodynamic parameters (ECG, systolic time intervals) were analyzed.
Main Results:
- Nifedipine did not significantly alter plasma concentrations or renal excretion of beta-acetyldigoxin or digitoxin.
- Heart rate and PQ interval remained unchanged, but T-wave flattening intensified and QT duration lengthened with nifedipine.
- Co-administration of nifedipine with beta-acetyldigoxin increased pre-ejection period index (PEPI) and PEP/LVET ratio, while digitoxin showed minimal changes in systolic time intervals.
Conclusions:
- Nifedipine exhibits no clinically significant impact on the pharmacokinetics of beta-acetyldigoxin or digitoxin.
- While some minor pharmacodynamic changes were observed, nifedipine does not appear to significantly alter the overall efficacy or safety profile of these cardiac glycosides.