Skip to main content
SpringerLink
Log in

Pharmakokinetik und kardiale Wirksamkeit von β-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Nifedipin

Effects of nifedipine on pharmacokinetics and pharmacodynamics of β-acetyldigoxin and digitoxin in patients

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

The effect of nifedipine (N) on the pharmacokinetics and pharmacodynamics of β-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 (QS2I), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET-ratio were recorded repeatedly before and during coadministration 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  1. Bazett HC (1920) An analysis of the time relations of the electrocardiogram. Heart 7:353

    Google Scholar 

  2. Belz GG, Riedlinger G (1980) Nicht invasive Untersuchungen zur kardialen Wirkung niedriger Digitoxin-Erhaltungsdosen. Z Kardiol 69:296

    Google Scholar 

  3. Belz GG, Doering W, Munkes R, Matthews J (1983) Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clin Pharmacol Ther 33:410

    Google Scholar 

  4. Doering W (1979) Quinidine-digoxin interaction: pharmacokinetics, underlying mechanisms and clinical implications. N Engl J Med 301:400

    Google Scholar 

  5. Ebner F (1977) Wirkung und Verträglichkeit von Adalat® bei Kombination mit verschiedenen Medikamenten. Münch med Wochenschr 199 [Suppl 1]:69

    Google Scholar 

  6. Ejvinsson G (1978) Effect of quinidine on plasma concentrations of digoxin. Br Med J 1:279

    Google Scholar 

  7. Fleckenstein A (1971) Specific inhibitors and promoters of calcium action in the excitation — coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: Harris P, Opie L (Hrsg) Calcium and the Heart. Academic Publishers, London New York, p 135

    Google Scholar 

  8. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149

    Google Scholar 

  9. Franke H (1983) Allgemeine und pharmakologische Therapieprinzipien bei betagten Patienten. In: Franke H (Hrsg) Gerotherapie. G Fischer, Stuttgart, S 5

    Google Scholar 

  10. Hager WD, Fenster P, Mayersohn M, Perrier D, Graves P, Marcus FJ, Goldman St (1979) Digoxin-quinidine interaction: Pharmacokinetic evaluation. N Engl J Med 300:1238

    Google Scholar 

  11. Henry PhD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047

    Google Scholar 

  12. Hess OM, Hirzel HO, Krayenbühl HP (1982) Calcium-Antagonisten in der Behandlung von Herzkrankheiten. Schweiz med Wschr 112:689

    Google Scholar 

  13. Hooymans PM, Merkus FWHM (1978) Effect of quinidine on plasma concentration of digoxin. Br Med J 2:1022

    Google Scholar 

  14. Karlsberg RP (1982) Calcium channel blockers for cardiovascular disorders. Arch intern Med 142:452

    Google Scholar 

  15. Klein HO, Lang R, Weiss E, Segni ED, Libhaber C, Guerrero J, Kaplinsky E (1982) The influence of verapamil on serum digoxin concentration. Circulation 65:998

    Google Scholar 

  16. Kreutz G, Keller F, Gast D, Prokein E (1982) Digitoxin — Quinidine interaction achieving steady — state conditions for both drugs. Naunyn — Schmiedeberg's Arch Pharmacol 319 [Suppl]:R82

  17. Kuhlmann J (1981) Calciumantagonisten. Dtsch Apoth Ztg 121:2890

    Google Scholar 

  18. Kuhlmann J (1983) Interaktionen mit Herzglykosiden und deren klinische Relevanz. Rietbrock N, Schnieders B, Schuster J (Hrsg) Symposium Nr. Y-5-813-080-2 „Wandlungen in der Therapie der Herzinsuffizienz.“ Vieweg, Braunschweig Wiesbaden, S 165

    Google Scholar 

  19. Kuhlmann J (1984) Klinische Relevanz von Arzneimittel-Interaktionen am Beispiel herzwirksamer Glykoside. Med Klin 79:150

    Google Scholar 

  20. Kuhlmann J, Marcin S (1983) Lack of significant effect of nifedipine and diltiazeme on the pharmacokinetics of digitoxin. Abstracts of the II. World Conference of Clinical Pharmacology and Therapeutics, Juli 31 – August 5, 1983, Washington D.C., p 136:792

  21. Kuhlmann J, Marcin S, Frank KH (1983) Effects of nifedipine and diltiazeme on the pharmacokinetics of digoxin. Abstracts Joint Meeting of the French and German Pharmacological and Toxicological Societies, September 19.–22., 1983, Freiburg i.Br. Naunyn-Schmiedeberg's Arch Pharmacol 324 [Suppl]:R81

  22. Kuhlmann J, Dohrmann M, Marcin S (1984) Effects of quinidine on plasma level and renal excretion of digitoxin achieving steady state conditions. Naunyn-Schmiedeberg's Arch Pharmacol 325 [Suppl]:R85

  23. Kuhlmann J, Reitinger A (1984) Intoxikationshäufigkeit von Digoxin und Digitoxin. Vergleichende Untersuchung über 2 Jahre an Patienten einer Medizinischen Universitätsklinik. Med Klin (in Vorbereitung)

  24. Kuhn H, Loogen F (1980) Die Bestimmung der systolischen Zeitintervalle. DMW 105:214

    Google Scholar 

  25. Leahey EB, Reiffel JA, Drusin RE, Heissenbuttel RH, Lovejoy WP, Bigger JT (1978) Interaction between quinidine and digoxin. JAMA 240:533

    Google Scholar 

  26. Lehmann HU, Hochrein H (1980) Indikationen der Calcium-Antagonisten. Med Klin 75:288

    Google Scholar 

  27. Meyer J (1983) Der Einsatz von Calciumantagonisten in der Therapie der koronaren Herzkrankheit. Internist 24:408

    Google Scholar 

  28. Nayler WG, Poole-Wilson Ph (1981) Calcium antagonists: definition and mode of action. Basic Res Cardiol. 76:1

    Google Scholar 

  29. Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F (1981) Digoxin-verapamil interaction. Clin Pharmacol Ther 30:311

    Google Scholar 

  30. Pedersen KE, Dorph-Pedersen A, Hvidt St, Klitgaard NA, Kjaer K, Nielsen-Kudsk F (1982) Effect of nifedipine on digoxin kinetics in healthy subjects. Clin Pharmacol Ther 32:562

    Google Scholar 

  31. Peters U, Risler T, Grabensee B, Falkenstein U, Krokou J (1980) Interaktion von Chinidin und Digitoxin beim Menschen. Dtsch med Wochenschr 105:438

    Google Scholar 

  32. Peters U, Risler T, Grabensee B, Falkenstein U (1981) Untersuchungen zur Interaktion von Chinidin und Digitoxin. In: Kochsiek K, Rietbrock N (Hrsg) Digitalistherapie bei Herzinsuffizienz. Urban & Schwarzenberg, München Wien Baltimore, S 136

    Google Scholar 

  33. Rameis H, Mayometschnigg D, Nakel E (1983) Effects of diltiazem on serum digoxin concentrations: evaluation of an interaction. Abstracts of the II. World Conference of Clinical Pharmacology and Therapeutics, Juli 31–August 5, 1983, Washington D.C., p 47:273

  34. Risler T, Peters U, Grabensee B, Seipel L, Krokou J (1979) Untersuchungen zur Interaktion von Chindin und Digoxin. Dtsch med Wochenschr 104:1523

    Google Scholar 

  35. Rosenthal J (1982) Kalzium-Antagonisten in der Differentialtherapie der arteriellen Hypertonie. Münch med Wochenschr 124:1047

    Google Scholar 

  36. Rowland E, Evans T, Krikler D (1979) Effect of nifedipine on atrioventricular conduction as compared with verapamil: intracardiac electrophysiological study. Br Heart J 42:124

    Google Scholar 

  37. Scholz H (1983) Calcium-Antagonisten in der Herztherapie. Dtsch med Wochenschr 108:767

    Google Scholar 

  38. Schwartz JB, Keefe D, Kates RE, Harrison DC (1981) Verapamil and digoxin: another drug-drug interaction. Clin Res 29:501A

    Google Scholar 

  39. Seipel L, Breithardt G, Borggrefe M (1983) Antiarrhythmische Therapie mit Calciumantagonisten. Internist 24:415

    Google Scholar 

  40. Steiness E (1974) Renal tubular secretion of digoxin. Circulation 50:103

    Google Scholar 

  41. Thiercelin JF, Hermann Ph, Warrington S, Thénot JP, Morselli PL (1983) Interaction study between digoxin and calcium antagonists: verapamil and diltiazem. Abstracts of the II. World Conference of Clinical Pharmacology and Therapeutics, Juli 31–August 5, 1983, Washington D.C., p 47:275

  42. Vöhringer HF, Rietbrock N, Spurny P, Kuhlmann J, Hampl H, Baethke R (1976) Disposition of digitoxin in renal failure. Clin Pharmacol Ther 19:387

    Google Scholar 

  43. Weissler AM, Harris WS, Schoenfeld CD (1968) Systolic time intervals in heart failure in man. Circulation 37:149

    Google Scholar 

  44. Weissler AM, Harris WS, Schoenfeld CD (1969) Beside techniques to evaluate ventricular function in man. Am J Cardiol 23:577

    Google Scholar 

  45. Weissler AM (1977) Current concepts in cardiology: Systolic time intervals. N Engl J Med 296:321

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Univ.-Klinik Würzburg, Germany

    J. Kuhlmann, S. Marcin & K. H. Frank

Authors
  1. J. Kuhlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Marcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. H. Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuhlmann, J., Marcin, S. & Frank, K.H. Pharmakokinetik und kardiale Wirksamkeit von β-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Nifedipin. Klin Wochenschr 62, 451–457 (1984). https://doi.org/10.1007/BF01726906

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01726906

Key words

Search

Navigation