Summary
The effect of two different doses of nitrendipine on plasma digoxin levels, urinary recovery and systolic time intervals was investigated in 8 healthy volunteers. Following a loading dose, digoxin 0.25 mg b.d. p.o. was given alone for 2 weeks. Then 0.25 mg digoxin b.d. was administered for two 1-week periods combined with nitrendipine 10 mg or 20 mg once daily. The study was completed with another digoxin monotherapy phase lasting 7 days. Nitrendipine 20 mg daily led to a significant increase in plasma digoxin levels and in its area under the plasma concentration-time curve AUC (0–12) compared to digoxin monotherapy. The AUC (0–12) was 9.7 ng ml−1h when digoxin alone was given and 11.2 ng ml−1h on co-administration of the calcium antagonist. Urinary recovery and renal clearance of digoxin were slightly but not significantly increased by nitrendipine. Nitrendipine 10 mg once daily caused a small, insignificant tendency to elevate the plasma digoxin level. Nitrendipine co-administration (10 and 20 mg once daily) did not significantly alter systolic time intervals, as non-invasively measured haemodynamic parameters, compared to digoxin treatment alone. Thus, nitrendipine 20 mg daily caused a significant increase in plasma digoxin concentrations and in its AUC, which would rarely be of clinical relevance.
Similar content being viewed by others
References
Belz GG, Aust PE, Doering W, Heinz M, Schneider B (1982a) Pharmacodynamics of a single dose of quinidine during chronic digoxin treatment — a randomized double blind placebo and sparteine controlled crossover study. Eur J Clin Pharmacol 22: 112–117
Belz GG, Doering W, Munkes R, Matthews J (1983) Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clin Pharmacol Ther 33: 410–417
Belz GG, Doering W, Aust PE, Heinz M, Matthews J, Schneider B (1982b) Quinidine-digoxin interaction: cardiac efficacy of elevated serum digoxin concentration. Clin Pharmacol Ther 31: 548–554
Belz GG, Wistuba S, Matthews JH (1986) Digoxin and bepridil: Pharmacokinetic and pharmacodynamic interactions. Clin Pharmacol Ther 39: 65–71
Erbel R, Belz GG (1977) Untersuchungen zur Meßmethode der systolischen Zeitintervalle. Z Kardiol 66: 433–435
Kirch W, Hutt HJ, Heidemann H, Rämsch K, Janisch HD, Ohnhaus EE (1984) Drug interactions with nitrendipine. J Cardiovasc Pharmacol 6 [Suppl 7]: S982-S985
Kirch W, Hutt HJ, Dylewicz P, Gräf KJ, Ohnhaus EE (1986a) Dose dependence of the nifedipine/digoxin interaction? Clin Pharmacol Ther 39: 35–39
Kirch W, Stenzel J, Dylewicz P, Hutt HJ, Santos SR, Ohnhaus EE (1986b) Influence of nisoldipine on haemodynamic effects and plasma levels of digoxin. Br J Clin Pharmacol 22: 155–159
Kirch W, Ohnhaus EE, Dylewicz P, Pabst J, Storstein L (1986) Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency. Am Heart J 111: 325–329
Kleinbloessem CH, Brummelen van P, Hillers J, Moolenaar AJ, Breimer DD (1985) Interaction between digoxin and nifedipine at steady-state in patients with atrial fibrillation. Ther Drug Monit 7: 372–376
Kuhlmann J (1985) Effects of nifedipine and diltiazem on levels and renal excretion of beta-acetyldigoxin. Clin Pharmacol Ther 37: 150–156
Oesterle SN, Schroeder JS (1982) Calcium-entry blockade, beta-adrenergic blockade and the reflex control of circulation. Circulation 65: 669–670
Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Kjaer K, Nielson-Kudski F (1981) Effect of nifedipine on digoxin kinetics in healthy subjects. Clin Pharmacol Ther 32: 562–565
Robson RH, Vishwanath MC (1982) Nifedipine and beta-blockade as a cause of cardiac failure. Br Med J 284: 104
Sachs L (1983) Angewandte Statistik, 6th edn, Springer, Berlin Heidelberg New York
Schäfer SG, Schuhmann G, Doering W, Fichtl B (1985) Influence of quinidine on the intestinal secretion of digoxin and digitoxin in guinea pigs. Chem Biol Interact 55: 203–213
Schwartz JB, Migliore PJ (1984) Effect of nifedipine on serum digoxin concentration and renal digoxin clearance. Clin Pharmacol Ther 36: 19–24
Walsh RA, Badke ER, O'Rourke RA (1981) Differential effects of systemic and intracoronary calcium channel blocking agents on global and regional left ventricular function in conscious dogs. Am Heart J 102: 341–350
Weissler AM, Harris WS, Schoenfeld CD (1968) Systolic time intervals in heart failure in man. Circulation 37: 149–159
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kirch, W., Logemann, C., Heidemann, H. et al. Effect of two different doses of nitrendipine on steady-state plasma digoxin level and systolic time intervals. Eur J Clin Pharmacol 31, 391–395 (1986). https://doi.org/10.1007/BF00613512
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00613512