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Pharmacokinetic Interactions with Digoxin

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  • Pharmacokinetic Drug Interactions
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Summary

Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin. Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin. Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients. Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets.

Various drugs induce alterations in the volume of distribution and clearance of digoxin. Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents. Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.

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References

  • Achilli A, Serra N. Amiodarone increases plasma digoxin concentrations. Correspondence. British Medical Journal 282: 1630, 1981

    Article  PubMed  CAS  Google Scholar 

  • Albert KS, Ayres JW, DiSanta AR, et al. Influence of kaolinpectin suspension on digoxin bioavailability. Journal of Pharmaceutical Sciences 67: 1582–1586, 1978

    Article  PubMed  CAS  Google Scholar 

  • Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium-aluminum hydroxide and kaolin-pectin on absorption of digoxin from tablets and capsules. Journal of Clinical Pharmacology 21: 26–30, 1981

    PubMed  CAS  Google Scholar 

  • Andrejak M, Nary L, Andrejak MT, Lesbre J. Diltiazem increases steady-state digoxin levels in patients with cardiac disease. Journal of Clinical Pharmacology 27: 967–970, 1987

    PubMed  CAS  Google Scholar 

  • Angelin B, Avvidssen A, Dahlqvist R, Hedman A, Schenck-Gustafsson K. Quinidine reduces biliary clearance of digoxin in man. European Journal of Clinical Investigations 17: 262–265, 1987

    Article  CAS  Google Scholar 

  • Antman E, Arnold M, Friedman P, Smith T. Pharmacokinetic drug interactions between digoxin and antiarrhythmic agents and calcium blocking agents: an appraisal of study methodology. Cardiovascular Drugs and Therapy 1: 183–189, 1987

    Article  PubMed  CAS  Google Scholar 

  • Baciewicz AM, Self TH. Rifampin drug interaction. Archives of Internal Medicine 144: 1667–1671, 1984

    Article  PubMed  CAS  Google Scholar 

  • Beltrami T, May J, Bertino J. Lack of effects of diltiazem on digoxin pharmacokinetics. Journal of Clinical Pharmacology 25: 390–392, 1985

    PubMed  CAS  Google Scholar 

  • Belz GG, Doering W, Munkes R, Matthews J. Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clinical Pharmacology and Therapeutics 33: 410–417, 1983

    Article  PubMed  CAS  Google Scholar 

  • Belz GG, Doering W, Munkes R, et al. Effects of various calciumantagonists on blood level and renal clearance of digoxin. Circulation 64 (Suppl. IV): 24, 1981

    Google Scholar 

  • Belz GG, Doering W, Aust PE, et al. Quinidine-digoxin interaction: cardiac efficacy of elevated serum digoxin concentration. Clinical Pharmacology and Therapeutics 31: 548–554, 1982

    Article  PubMed  CAS  Google Scholar 

  • Bigger Jr JT. The quinidine-digoxin interaction. Modern Concepts of Cardiovascular Disease 51: 73–78, 1982

    PubMed  Google Scholar 

  • Bigger Jr JT, Leahey Jr EG. Quinidine and digoxin: an important interaction. Drugs 24: 220–239, 1982

    Article  Google Scholar 

  • Binnion PF. Absorption of different commercial preparations of digoxin in the normal human subject and the influence of antacid, antidiarrhoeal and ion-exchange resins. In Storstein (Ed.) Symposium on digitalis, pp. 216–224, Glydendal Norsk Forlag, Oslo, 1973

  • Bjornsson T, Huang A, Roth P, Jacob D, Christenson R. Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations. Clinical Pharmacology and Therapeutics 39: 25–28, 1986

    Article  PubMed  CAS  Google Scholar 

  • Brown DD, Dormois JD, Abraham GN, et al. Effect of furosemide on the renal excretion of digoxin. Clinical Pharmacology and Therapeutics 20: 395–400, 1976

    PubMed  CAS  Google Scholar 

  • Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. New England Journal of Medicine 295: 1034–1037, 1976

    Article  PubMed  CAS  Google Scholar 

  • Brown DD, Juhl RP, Warner SL. Decreased bioavailability of digoxin due to hypocholesterolemic interventions. Circulation 58: 164–172, 1978

    Article  PubMed  CAS  Google Scholar 

  • Brown DD, Juhl RP, Warner SL. Effects of hypocholesterolemic interventions on digoxin bioavailability. Drug Metabolism Reviews 9: 107–117, 1979

    PubMed  CAS  Google Scholar 

  • Brown DD, Schmid J, Long RA, Hull JH. A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules. Journal of Clinical Pharmacology 25: 360–364, 1985

    PubMed  CAS  Google Scholar 

  • Brown DD, Spector R, Juhl RP. Drug interactions with digoxin. Drugs 20: 198–206, 1980

    Article  PubMed  CAS  Google Scholar 

  • Bussey HI. The influence of quinidine and other agents on digitalis glycosides. American Heart Journal 104: 289–302, 1982

    Article  PubMed  CAS  Google Scholar 

  • Caldwell JH, Bush CA, Greenberger NJ. Interruption of the enterohepatic circulation of digitoxin by cholestyramine. Journal of Clinical Investigation 50: 2638–2644, 1971

    Article  PubMed  CAS  Google Scholar 

  • Castillo-Ferrando JR, Garcia M, Carmona J. Digoxin levels and diazepam. Lancet 2: 368, 1980

    Article  PubMed  CAS  Google Scholar 

  • Chapple DJ, Hughes R, Johnson BF. The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs. British Journal of Pharmacology 57: 23–27, 1976

    Article  PubMed  CAS  Google Scholar 

  • Chen TS, Friedman HS. Alteration of digoxin pharmacokinetics by a single dose of quinidine. Journal of the American Medical Association 244: 669–672, 1980

    Article  PubMed  CAS  Google Scholar 

  • Cleland J, Dargie H, Pettigrew A, Gillen G, Robertson J. The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure. American Heart Journal 112: 130–135, 1986

    Article  PubMed  CAS  Google Scholar 

  • Cogan JJ, Humphreys MD, Carlson CJ, et al. Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Circulation 64: 973–978, 1981

    Article  PubMed  CAS  Google Scholar 

  • Cohn J, Archibald D, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. New England Journal of Medicine 314: 1547–1552, 1986

    Article  PubMed  CAS  Google Scholar 

  • Coltart J, Howard M, Chamberlain D. Myocardial and skeletal muscle concentrations of digoxin in patients on long-term therapy. British Medical Journal 2: 318–319, 1972

    Article  PubMed  CAS  Google Scholar 

  • Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. New England Journal of Medicine 316: 1429–1435, 1987

    Article  Google Scholar 

  • Crome P, Curl B, Holt D, Volcano G, Bennett P, et al. Digoxin and cimetidine: investigation of the potential for a drug interaction. Human Toxicology 4: 391–399, 1985

    Article  PubMed  CAS  Google Scholar 

  • Dahlqvist R, Ejvinsson G, Schenck-Gustafsson K. Effect of quinidine on plasma concentration and renal clearance of digoxin: a clinically important drug interaction. British Journal of Clinical Pharmacology 9: 413–418, 1980

    Article  PubMed  CAS  Google Scholar 

  • Das G, Barr CE, Carlson J. Reduction of digoxin effect during the digoxin-quinidine interaction. Clinical Pharmacology and Therapeutics 35: 317–321, 1984

    Article  PubMed  CAS  Google Scholar 

  • Day T, Hunt D. Interaction between mexiletine and digoxin. Medical Journal of Australia 2: 630, 1983

    PubMed  CAS  Google Scholar 

  • DiPiro JT, Cote JR, DiPiro CR, et al. Spironolactone interference with digoxin radioimmunoassay in cirrhotic patients. American Journal of Hospital Pharmacy 37: 1518–1521, 1980

    PubMed  CAS  Google Scholar 

  • Dobkin JF, Saha JR, Butler VP. Digoxin-inactivating bacteria: identification in human gut flora. Science 220: 325–327, 1983

    Article  CAS  Google Scholar 

  • Doering W. Quinidine-digoxin interaction: pharmacokinetics, underlying mechanism and clinical implications. New England Journal of Medicine 301: 400–404, 1979

    Article  PubMed  CAS  Google Scholar 

  • Doering W. Is there a clinically relevant interaction between quinine and digoxin in human beings? American Journal of Cardiology 48: 975–976, 1981

    Article  PubMed  CAS  Google Scholar 

  • Doering W, Belz GG. Quinidine-digoxin interaction: effect of quinidine on 86Rb-uptake of human erythrocytes. Klinische Wochenschrift 59: 95–96, 1981

    Article  PubMed  CAS  Google Scholar 

  • Doering W, Fichtl B, Herrmann M, et al. Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism. European Journal of Clinical Pharmacology 21: 281–285, 1982

    Article  PubMed  CAS  Google Scholar 

  • Doering VW, Isbary J. Der einfluss von tiaprofensaure auf diet digoxin-konzentration mim serum. Arzneimittel-Forschung Drug Research 33: 167–168, 1983

    CAS  Google Scholar 

  • Doering W, Konig E. Chinidin erhoht den Digoxin-Spiegel. Medizinische Klinik 76: 395–398, 1981

    PubMed  CAS  Google Scholar 

  • Doering W, Maass L, Irmisch R, Konig E. Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers. American Journal of Cardiology 59: 60D–64D, 1987

    Article  PubMed  CAS  Google Scholar 

  • Doherty JE. The digoxin-quinidine interaction. Annual Review of Medicine 33: 163–170, 1982

    Article  PubMed  CAS  Google Scholar 

  • Douste-Blazy P, Blanc M, Mantastruc J, Conte D, Cotonat J, et al. Is there any interaction between digoxin and enalapril? British Journal of Clinical Pharmacology 22: 752–753, 1986

    Article  PubMed  CAS  Google Scholar 

  • Ejvinsson G. Effect of quinidine on plasma concentrations of digoxin. British Medical Journal 1: 279–280, 1978

    Article  PubMed  CAS  Google Scholar 

  • Elkayam U, Parikh K, Torkan B, Weber L, Cohen J, et al. Effect of diltiazem on renal clearance and serum concentration of digoxin in patients with cardiac disease. American Journal of Cardiology 55: 1393–395, 1985

    Article  PubMed  CAS  Google Scholar 

  • Fenster PE, Comess KA, Hanson CD, et al. Kinetics of the digoxin-aspirin combination. Clinical Pharmacology and Therapeutics 32: 428–430, 1982a

    Article  PubMed  CAS  Google Scholar 

  • Fenster PE, Hager WD, Goodman MM. Digoxin-quinidine-spironolactone interaction. Clinical Pharmacology and Therapeutics 36: 70–73, 1984

    Article  PubMed  CAS  Google Scholar 

  • Fenster PE, Hager WD, Perrier D, Powell JR, Graves PE, et al. Digoxin-quinidine interaction in patients with chronic renal failure. Circulation 66: 1277–1280, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Fenster PE, Powell R, Hager D, et al. Onset and dose dependence of the digoxin-quinidine interaction. American Journal of Cardiology 45: 413, 1980

    Article  Google Scholar 

  • Fenster PE, White Jr NW, Hanson CD. Pharmacokinetic evaluation of the digoxin-amiodarone interaction. Journal of the American College of Cardiology 5: 108–112, 1985

    Article  PubMed  CAS  Google Scholar 

  • Finch MB, Johnston GD, Kelly JG, et al. Pharmacokinetics of digoxin alone and in the presence of indomethacin therapy. British Journal of Clinical Pharmacology 17: 353–355, 1984

    Article  PubMed  CAS  Google Scholar 

  • Finnegan TP, Spence JD, Cape RD. Potassium-sparing diuretics: interaction with digoxin in elderly men. Geriatrics 32: 129–131, 1984

    CAS  Google Scholar 

  • Floyd RA. Digoxin interaction with bran and high fiber foods. American Journal of Hospital Pharmacy 35: 660, 1978

    PubMed  CAS  Google Scholar 

  • Fraley DS, Britton HL, Schwinghammer TL, et al. Effect of cimetidine on steady-state serum digoxin concentrations. Clinical Pharmacology 2: 163–165, 1983

    CAS  Google Scholar 

  • Friedman HS. Erythromycin-induced digoxin toxicity. Correspondence. Chest 82: 202, 1982

    Article  CAS  Google Scholar 

  • Friedman HS, Chen TS. Use of control steady-state serum digoxin levels for predicting serum digoxin concentration after quinidine administration. American Heart Journal 104: 72–76, 1982

    Article  PubMed  CAS  Google Scholar 

  • Furlanello F, Inama G, Ferrari M, et al. Un altro tipo di interazione fra livelli ematici della digitale e di farmaci antiaritmici: digoxena ed amiodarone. Giornale Italiano di Cardiologia 11: 1725–1728, 1981

    PubMed  CAS  Google Scholar 

  • Garty M, Perry G, Shmueli H, Ilfeld D, Boser G, et al. Effect of cimetidine on digoxin disposition in peptic ulcer patients. European Journal of Clinical Pharmacology 30: 489–491, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gault H, Longerich L, Dawe M, Fine A. Digoxin-rifampin interaction. Clinical Pharmacology and Therapeutics 35: 750–754, 1984

    Article  PubMed  CAS  Google Scholar 

  • George CF, Renwick AG. Quinidine and the non-renal elimination of digoxin. Journal of Pharmacy and Pharmacology 34: 280, 1982

    Article  PubMed  CAS  Google Scholar 

  • Gessman L, Danilo P, Rosen MR. An electrophysiologic study of the digoxin-quinidine interaction. Journal of Clinical Pharmacology 23: 16–23, 1983

    PubMed  CAS  Google Scholar 

  • Gibson TP, Quintanilla A. Effect of quinidine on the renal handling of digoxin. Journal of Laboratory and Clinical Medicine 96: 1062, 1980

    PubMed  CAS  Google Scholar 

  • Goldman RH, Deutscher RN, Schweizer E, et al. Effect of a pharmacologic dose of digoxin on inotropy in hyper- and normokalemic dogs. Arr erican Journal of Physiology 223: 1438, 1972

    CAS  Google Scholar 

  • Hager WD, Fenster P, Mayersohn M, et al. Digoxin-quinidine interaction: pharmacokinetic evaluation. New England Journal of Medicine 300: 1238–1241, 1979

    Article  PubMed  CAS  Google Scholar 

  • Hager WD, Mayersohn M, Graves PE. Digoxin bioavailability during quinidine administration. Clinical Pharmacology and Therapeutics 30: 594–599, 1981

    Article  PubMed  CAS  Google Scholar 

  • Hall WH, Shappell JD, Doherty JE. Effect of cholestyramine on digoxin absorption and excretion in man. American Journal of Cardiology 39: 213–216, 1977

    Article  PubMed  CAS  Google Scholar 

  • Hartel G, Manninen V, Reisell P. Treatment of digoxin intoxication. Lancet 2: 158, 1973

    Article  PubMed  CAS  Google Scholar 

  • Hirschberg R, Schaefer K, Von-Herrath D, et al. Digoxin-quinidine interaction in patients with renal failure. Klinische Wochenschrift 59: 521–522, 1981

    Article  PubMed  CAS  Google Scholar 

  • Hirsh PD, Winer HJ, North RL. Further insights into digoxinquinidine interaction: lack of correlation between serum digoxin concentration and inotropic state of the heart. American Journal of Cardiology 46: 863–868, 1980

    Article  PubMed  CAS  Google Scholar 

  • Hooymans PM, Merkus FWHM. Effect of quinidine on plasma concentration of digoxin. British Medical Journal 2: 1022, 1978

    Article  PubMed  CAS  Google Scholar 

  • Hooymans PM, Merkus FWHM. Current status of cardiac glycoside drug interactions. Clinical Pharmacy 4: 404–413, 1985

    PubMed  CAS  Google Scholar 

  • Horn JM. Spironolactone and digoxin. Drug Interactions Newsletter 2: 51: 54, 1982

    Google Scholar 

  • Hutt H, Kirch W, Dylewicz P, Ohnhaus E. Dose-dependence of the nifedipine-digoxin interaction? Archives of Toxicology 9 (Suppl.): 209–212, 1986

    Article  PubMed  CAS  Google Scholar 

  • Isbary J, Doering W, Konig E. Der einfluss von tiaprofensaure auf die digoxinkonzentration im serum im vergleich zu anderen antirheumatika. Zeitschrift für Rheumatologie 41: 164, 1982

    Google Scholar 

  • Johnson BF, Bustrack J, Urbach D, Hull JH, Marwaha R. Effect of metoclopramide on digoxin absorption from tablets and capsules. Clinical Pharmacology and Therapeutics 36: 724–730, 1984

    Article  PubMed  CAS  Google Scholar 

  • Johnson BF, O’Grady J, Bye C. The influence of digoxin particle size on absorption of digoxin and the effect of propantheline and metoclopramide. British Journal of Clinical Pharmacology 5: 465–467, 1978

    Article  PubMed  CAS  Google Scholar 

  • Johnson BF, Rodin SM, Hoch K, Shekar V. The effect of dietary fiber on the bioavailability of digoxin in capsules. Journal of Clinical Pharmacology 27: 487–490, 1987a

    PubMed  CAS  Google Scholar 

  • Johnson BF, Wilson J, Marwaha R, Hoch K, Johnson J. The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics. Clinical Pharmacology and Therapeutics 42: 66–71, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Jones WN, Korn K, Rindone J, Mayersohn M, Bliss M, et al. Digoxin-diltiazem interactions: a pharmacokinetic evaluation. European Journal of Clinical Pharmacology 31: 351–353, 1986

    Article  PubMed  CAS  Google Scholar 

  • Jordaens L, Hoegaerts J, Belpaire E. Non-interaction of cimetidine with digoxin absorption. Acta Clinica Belgica 36: 109–110, 1981

    PubMed  CAS  Google Scholar 

  • Juhl RP, Summers RW, Guillory JK, et al. Effect of sulphasalazine on digoxin bioavailability. Clinical Pharmacology and Therapeutics 20: 387–394, 1976

    PubMed  CAS  Google Scholar 

  • Kaplinsky C, Aladjem M, Wolfish N, et al. Digoxin-quinidine interaction: in vitro studies in rat tissue. Journal of Laboratory and Clinical Medicine 96: 592, 1980

    PubMed  CAS  Google Scholar 

  • Kayser S. Drugs increasing digoxin serum concentrations. Drug Interaction Newsletter 5: 1–6, 1985

    Google Scholar 

  • Kennedy HL, Sprague MK, Redd RM, Wiens R, Blum R, et al. Serum digoxin concentrations during ethmozine antiarrhythmia therapy. American Heart Journal 111: 667, 1986

    Article  PubMed  CAS  Google Scholar 

  • Keren G, Tepper D, Butler B, et al. Studies on the possible mechanism of lidoflazine arrhythmogenicity. Journal of the American College of Cardiology 4: 742–747, 1984

    Article  PubMed  CAS  Google Scholar 

  • Khalil SAH. The uptake of digoxin and digitoxin by some antacids. Journal of Pharmacy and Pharmacology 26: 961–967, 1974

    Article  PubMed  CAS  Google Scholar 

  • Kilgore TL, Lehman CR. Treatment of digoxin intoxication with colestipol. Southern Medical Journal 75: 1259, 1982

    Article  PubMed  CAS  Google Scholar 

  • Kirch W, Hutt HJ, Dylewicz P, Graf JK, Ohnhaus EE. Dose-dependence of the nifedipine-digoxin interaction? Clinical Pharmacology and Therapeutics 39: 35–39, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kirch W, Hutt M, Heidemann H, Ramsch K, Janesch H, et al. Drug interactions with nitrendipine. Journal of Cardiovascular Pharmacology 6: S982–S985, 1984

    Article  PubMed  CAS  Google Scholar 

  • Klein HO, Lang R, Weiss E, et al. The influence of verapamil on serum digoxin concentration. Circulation 65: 998–1003, 1982

    Article  PubMed  CAS  Google Scholar 

  • Klein H, Pauzner H, DiSegni E, David D, Kaplinski E. The beneficial effects of verapamil in chronic atrial fibrillation. Archives of Internal Medicine 139: 747–749, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kleinbloesem C, van Brummelen P, Hillers J, Moolenaas A, Breimer D. Interaction between digoxin and nifedipine at steady-state in patients with atrial fibrillation. Therapeutic Drug Monitoring 7: 372–376, 1985

    Article  PubMed  CAS  Google Scholar 

  • Koren G. Interaction between digoxin and commonly coadministered drugs on children. Pediatrics 75: 1032–1037, 1985

    PubMed  CAS  Google Scholar 

  • Koren G, Zylber-Katz E, Granit L, Levy M. Pharmacokinetic studies of nifedipine and digoxin co-administration. International Journal of Clinical Pharmacology, Therapy and Toxicology 24: 39–42, 1986

    CAS  Google Scholar 

  • Kuhlmann J. Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta-acetyldigoxin. Clinical Pharmacology and Therapeutics 37: 150–156, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kuhlmann J, Zilly W, Wilke J. Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin. Clinical Pharmacology and Therapeutics 30: 518–527, 1981

    Article  PubMed  CAS  Google Scholar 

  • Lang R, Klein H, DiSegni D, et al. Verapamil improves exercise capacity in chronic atrial fibrillation: double-blind cross-over study. American Heart Journal 105: 820–825, 1983

    Article  PubMed  CAS  Google Scholar 

  • Leahey Jr EG, Bigger Jr JT, Butler Jr VP, et al. Quinidine-digoxin interaction: time course and pharmacokinetics. American Journal of Cardiology 48: 1141–1146, 1981

    Article  PubMed  CAS  Google Scholar 

  • Leahey Jr EB, Carson JA, Bigger Jr JT, et al. Reduced renal clearance of digoxin during chronic quinidine administration. Circulation 60: 11–16, 1979a

    Google Scholar 

  • Leahey Jr EB, Reiffel JA, Drusin RE, et al. Interaction between quinidine and digoxin. Journal of the American Medical Association 240: 533–534, 1978

    Article  PubMed  Google Scholar 

  • Leahey Jr EB, Reiffel JA, Giardina EG, et al. The effect of quinidine and other oral antiarrhythmic drugs on serum digoxin: a prospective study. Annals of Internal Medicine 92: 605–608, 1980

    PubMed  Google Scholar 

  • Leahey Jr EB, Reiffel JA, Heissenbuttel RH, et al. Enhanced cardiac effect of digoxin during quinidine treatment. Archives of Internal Medicine 139: 519–521, 1979b

    Article  PubMed  Google Scholar 

  • Lessem J, Bellinetto A. Interaction between digoxin and the calcium antagonists nicardipine and tiapamil. Clinical Therapeutics 5: 595–602, 1983

    PubMed  CAS  Google Scholar 

  • Lewis GP, Holtzman JL. Interaction of flecainide with digoxin and propranolol. American Journal of Cardiology 53: 52–57B, 1984

    Article  CAS  Google Scholar 

  • Lichey J, Schroder R, Rietbrock N. The effect of oral spironolactone and intravenous canrenoate-K on the digoxin radioimmunoassay. International Journal of Clinical Pharmacology and Biopharmacy 15: 557–559, 1977

    PubMed  CAS  Google Scholar 

  • Lindenbaum J, Maulitz RM, Butler VP. Inhibition of digoxin absorption by neomycin. Gastroenterology 71: 399–404, 1976

    PubMed  CAS  Google Scholar 

  • Lindenbaum J, Rund DG, Butler Jr VP, et al. Inactivation of digoxin by the gut florae reversal by antibiotic therapy. New England Journal of Medicine 305: 789–794, 1981a

    Article  PubMed  CAS  Google Scholar 

  • Lindenbaum J, Tse-Eng D, Butler Jr VP, Rund DG. Urinary excretion of reduced metabolites of digoxin. American Journal of Medicine 71: 67–74, 1981b

    Article  PubMed  CAS  Google Scholar 

  • Lohman JJ, Hooymans PM, Verhey MT, et al. The effect of to-cainide on digoxin serum level and renal clearance. Pharmaceutisch Weekblad — Scientific Edition 5: 346, 1983

    Google Scholar 

  • MacFarland R, Moeller VR, Pieniaszek Jr HJ, Whitney Jr CC, Marcus FI. Assessment of the potential pharmacokinetic interaction between digoxin and ethmozine. Journal of Clinical Pharmacology 25: 138–143, 1985

    PubMed  CAS  Google Scholar 

  • Malcolm AD, Leung FY, Fuchs JCA, Duarte JE. Digoxin kinetics during furosemide administration. Clinical Pharmacology and Therapeutics 21: 567–574, 1977

    PubMed  CAS  Google Scholar 

  • Manninen V, Apajalahti A, Melin J, et al. Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1: 398–400, 1973

    Article  PubMed  CAS  Google Scholar 

  • Manolas EG, Hunt D, Sloman G. Effects of quinidine and disopyramide on serum digoxin concentrations. Australian and New Zealand Journal of Medicine 10: 426–429, 1980

    Article  PubMed  CAS  Google Scholar 

  • Marcus F. Pharmacokinetic interactions between digoxin and other drugs. Journal of the American College of Cardiology 5: 82A–90A, 1985

    Article  PubMed  CAS  Google Scholar 

  • Miyakawa T, Kobayashi L, Shionoiri H. The effect of captopril on serum digoxin concentration in patients with mild congestive heart failure. Abstract. Circulation 76: IV–86, 1987

    Google Scholar 

  • Moysey JO, Jaggarao NS, Grundy EN, et al. Amiodarone increases plasma digoxin concentrations. British Medical Journal 282: 272, 1981

    Article  PubMed  CAS  Google Scholar 

  • Mungall DR, Robichaux RP, Perry W, et al. Effects of quinidine on serum digoxin concentration. Annals of Internal Medicine 93: 689–693, 1980

    PubMed  CAS  Google Scholar 

  • Naafs MAB, Van der Hoek C, Schopman W, Van Duin S, Koorevaar G, et al. Renal clearance of digoxin in man after sodium loading or furosemide treatment. European Journal of Clinical Pharmacology 25: 375–379, 1983

    Article  PubMed  CAS  Google Scholar 

  • Nademanee K, Kannan R, Hendrickson J, Ookhtens M, Kay I, et al. Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications. Journal of the American College of Cardiology 4: 111–116, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nager G, Nager F. Interaktion zwischen amiodaron und digoxin. Schweizerische Medizinische Wochenschrift 113: 1727–1730, 1983

    PubMed  CAS  Google Scholar 

  • Neuvonen PJ, Elfving SM, Elonen E. Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man. European Journal of Clinical Pharmacology 13: 213–218, 1978

    Article  PubMed  CAS  Google Scholar 

  • Novi C, Bissoli F, Simonati V, et al. Rifampin and digoxin: possible drug interaction in a dialysis patient. Journal of the American Medical Association 244: 2521–2522, 1980

    Article  PubMed  CAS  Google Scholar 

  • Ochs HR, Bodem G, Greenblatt DJ. Impairment of digoxin clearance by coadministration of quinidine. Journal of Clinical Pharmacology 21: 396–400, 1981

    PubMed  CAS  Google Scholar 

  • Ochs HR, Gugler R, Guthoff T, et al. Effect of cimetidine on digoxin kinetics and creatinine clearance. American Heart Journal 107: 170–172, 1984

    Article  PubMed  CAS  Google Scholar 

  • Oetgen WJ, Sobol SM, Tri TB, Heydorn WH, Rakita L. Amiodarone-digoxin interaction, clinical and experimental observations. Chest 86: 75–79, 1984

    Article  PubMed  CAS  Google Scholar 

  • Oyama Y, Fujii S, Kanda K, et al. Digoxin-diltiazem interaction. American Journal of Cardiology 53: 1480–1481, 1984

    Article  PubMed  CAS  Google Scholar 

  • Payne VW, Secter RA, Noback RK. Use of colestipol in a patient with digoxin intoxication. Drug Intelligence and Clinical Pharmacy 15: 902–903, 1981

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Christiansen BD, Kjaer K, Klitgaard NA, Nielsen-Kudsk F. Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration. Clinical Pharmacology and Therapeutics 34: 8–13, 1983a

    Article  PubMed  CAS  Google Scholar 

  • Pedersen KE, Christiansen BD, Klitgaard NA, Nielsen-Kudsk F. Effect of quinidine on digoxin bioavailability. European Journal of Clinical Pharmacology 24: 41–47, 1983b

    Article  PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pedersen A, Hvidt S, et al. Digoxin-verapamil interaction. Clinical Pharmacology and Therapeutics 30: 311–316, 1981

    Article  PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pedersen A, Hvidt S, et al. The long-term effect of verapamil on plasma digoxin concentration and renal digoxin concentration and renal digoxin clearance in healthy subjects. European Journal of Clinical Pharmacology 22: 123–127, 1982a

    Article  PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pedersen A, Hvidt S, et al. Effect of nifedipine on digoxin kinetics in healthy subjects. Clinical Pharmacology and Therapeutics 32: 562–565, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Pedersen KE, Hastrup J, Hvidt S. The effect of quinidine on digoxin kinetics in cardiac patients. Acta Medica Scandinavica 207: 291–295, 1980

    Article  PubMed  CAS  Google Scholar 

  • Pedersen K, Madsen J, Klitgaard N, Kjoer K, Hvidt S. Non-interaction between nifedipine and digoxin. Danish Medical Bulletin 33: 109–110, 1986

    PubMed  CAS  Google Scholar 

  • Powell JR, Fenster PE, Hager WD, et al. Quinidine-digoxin interaction. Correspondence. New England Journal of Medicine 302: 176–177, 1980

    CAS  Google Scholar 

  • Quattrocchi FP, Robinson JD, Curry RW, et al. The effect of ibuprofen on serum digoxin concentration. Drug intelligence and Clinical Pharmacy 17: 286–288, 1983

    PubMed  CAS  Google Scholar 

  • Rameis H, Magometschnigg D, Ganzinger U. The diltiazem-digoxin interaction. Clinical Pharmacology and Therapeutics 36: 183–189, 1984

    Article  PubMed  CAS  Google Scholar 

  • Reissell P, Manninen V. Effect of administration of activated charcoal and fibre on absorption, excretion and steady-state blood levels of digoxin and digitoxin. Acta Medica Scandinavica 668 (Suppl.): 88–90, 1982

    PubMed  CAS  Google Scholar 

  • Risler T, Burk M, Peters U, Grabensee B, Seipel L. On the interaction between digoxin and disopyramide. Clinical Pharmacology and Therapeutics 34: 176–180, 1983

    Article  PubMed  CAS  Google Scholar 

  • Rodin S, Johnson BF, Wilson J, Ritchie P, Johnson J. Comparative effects of verapamil and isradipine upon steady-state kinetics. Clinical Pharmacology and Therapeutics, in press, 1988

    Google Scholar 

  • Rund DG, Lindenbaum J, Dobkin JF, Butler VP, Saha JR. Decreased digoxin cardioinactive metabolites after administration of an encapsulated liquid concentrate. Clinical Pharmacology and Therapeutics 34: 738–743, 1983

    Article  PubMed  CAS  Google Scholar 

  • Santostasi G, Fantin M, Maragno I, Garon R, Basadonna O, et al. Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects. Journal of Cardiovascular Pharmacology 9: 385–390, 1987

    Article  PubMed  CAS  Google Scholar 

  • Schenck-Gustafsson K, Dahlqvist R. Pharmacokinetics of digoxin in patients subjected to the quinidine-digoxin interaction. British Journal of Clinical Pharmacology 11: 181–186, 1981a

    Article  PubMed  CAS  Google Scholar 

  • Schenck-Gustafsson K, Jogestrand T, Brodin LA, Nordlander R, Dahlqvist R. Cardiac effects of treatment with quinidine and digoxin alone and in combination. American Journal of Cardiology 51: 777–782, 1983

    Article  PubMed  CAS  Google Scholar 

  • Schenck-Gustafsson K, Jogestrand T, Nordlander R, et al. Effect of quinidine on digoxin concentration in skeletal muscle and serum in patients with atrial fibrillation: evidence for reduced binding of digoxin in muscle. New England Journal of Medicine 305: 209–211, 1981b

    Article  PubMed  CAS  Google Scholar 

  • Schenck-Gustafsson K, Juhlin-Dannfett A, Dahlqvist R. Renal function and digoxin clearance during quinidine therapy. Clinical Physiology 2: 401–404, 1982

    Article  PubMed  CAS  Google Scholar 

  • Schrager BR, Pina I, Frangi M, Applewhite S, Sequeira R, et al. Diltiazem, digoxin interaction. Circulation 68: III–368, 1983

    Google Scholar 

  • Schwartz JB, Migliore PJ. Effect of nifedipine on serum digoxin concentration and renal digoxin clearance. Clinical Pharmacology and Therapeutics 36: 19–24, 1984

    Article  PubMed  CAS  Google Scholar 

  • Schwartz JB, Raizner A, Akers S. The effect of nifedipine on serum digoxin concentrations in patients. American Heart Journal 107: 669–673, 1984

    Article  PubMed  CAS  Google Scholar 

  • Somberg JC, Wellins H, Maguire W, Muira D. Verapamil-digitalis interaction: effect on cardiac Purkinje fibers and myocardium. Abstract. American Journal of Cardiology 49: 1025, 1982

    Article  Google Scholar 

  • Sorkin EM, Clissold SP, Brogden RN. Nifedipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs 30: 182–274, 1985

    Article  PubMed  CAS  Google Scholar 

  • Steiness E. Renal tubular secretion of digoxin. Circulation 50: 103–107, 1974

    Article  PubMed  CAS  Google Scholar 

  • Steiness E. Suppression of renal excretion of digoxin in hypokalemic patients. Clinical Pharmacology and Therapeutics 23: 511–514, 1978

    PubMed  CAS  Google Scholar 

  • Steiness E, Waldorff S, Hansen PB, et al. Reduction of digoxin-induced inotropism during quinidine administration. Clinical Pharmacology and Therapeutics 27: 791–795, 1980

    Article  PubMed  CAS  Google Scholar 

  • Straub KD, Kane JJ, Bissen JK, et al. Alteration of digitalis binding by quinidine: a mechanism of digitalis-quinidine interaction. Circulation 58: 11–58, 1978

    Google Scholar 

  • Thompson WC. Relationship of in vitro binding of digoxin to its intestinal absorption in rats. Canadian Journal of Pharmacology 51: 832–834, 1973

    Article  CAS  Google Scholar 

  • Tilstone WJ, Semple PF, Lawson DH, et al. Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentaymcin. Clinical Pharmacology and Therapeutics 22: 389–394, 1977

    PubMed  CAS  Google Scholar 

  • Tjandramaga TB, Verbesselt A, Hecken A, et al. Oral digoxin pharmacokinetics during multiple-dose flecainide treatment. Archives Internationales de Pharmacodynamie et de Thérapie 260: 302–303, 1982

    PubMed  CAS  Google Scholar 

  • Vohringer HF, Kuhlmann J, Rietbrock N. Der einfluss von antacida auf die plasmakonzentration von digoxin beim menschen. Deutsche Medizinische Wochenschrift 101: 106–108, 1976

    Article  PubMed  CAS  Google Scholar 

  • Waldorff S, Andersen JD, Heeboll-Nielsen N, et al. Spironolactone-induced changes in digoxin kinetics. Clinical Pharmacology and Therapeutics 24: 162–167, 1978

    PubMed  CAS  Google Scholar 

  • Waldorff S, Berning J, Bush J, et al. Systolic time intervals during spironolactone treatment of digitalized and non-digitalized patients with ischaemic heart disease. European Journal of Clinical Pharmacology 21: 269–273, 1982

    Article  PubMed  CAS  Google Scholar 

  • Waldorff S, Hansen PB, Egeblad H, et al. Interactions between digoxin and potassium-sparing diuretics. Clinical Pharmacology and Therapeutics 33: 418–423, 1983

    Article  PubMed  CAS  Google Scholar 

  • Waldorff S, Hansen PB, Kjaergard H, et al. Amiloride-induced changes in digoxin dynamics and kinetics: abolition of digoxin-induced inotropism with amiloride. Clinical Pharmacology and Therapeutics 30: 172–176, 1981

    Article  PubMed  CAS  Google Scholar 

  • Walker AM, Cody RJ, Greenblatt DS. Drug toxicity in patients receiving digoxin and quinidine. American Heart Journal 105: 1025–1028, 1983

    Article  PubMed  CAS  Google Scholar 

  • Weeks C, Conard G, Kvam D, Fox J, Chang S, et al. The effect of flecainide acetate, a new anti-arrhythmic, on plasma digoxin levels. Journal of Clinical Pharmacology 26: 27–31, 1986

    PubMed  CAS  Google Scholar 

  • Weintraub MD, Lasagna L. Serum and tissue concentrations of digoxin: a clinical and pathologic analysis. Clinical Pharmacology and Therapeutics 14: 149–151, 1973

    Google Scholar 

  • Wellens HJJ, Gorgels AP, Braat SJ, Bar SW, Vanagt EJ, et al. Effects of oral disopyramide on serum digoxin levels: a prospective study. American Heart Journal 100: 934–935, 1980

    Article  PubMed  CAS  Google Scholar 

  • Winter ME. Basic clinical pharmacokinetics, p. 71, Applied Therapeutics Inc., Spokane, 1988

    Google Scholar 

  • Woods MN, Ingelfinger JA. Lack of effect of bran on digoxin absorption. Clinical Pharmacology and Therapeutics 26: 21–23, 1979

    PubMed  CAS  Google Scholar 

  • Yeh BK, Chiang B, Sung PK. Antiarrhythmic activity of K+-carrenoate in man. American Heart Journal 92: 308, 1976

    Article  PubMed  CAS  Google Scholar 

  • Yoshida A, Fujita M, Kurosawa N, et al. Effects of diltiazem on plasma level and urinary excretion of digoxin in healthy subjects. Clinical Pharmacology and Therapeutics 35: 681–685, 1984

    Article  PubMed  CAS  Google Scholar 

  • Zoller B, Engel JH, Faust-Tinnefeldt G, Geissler HE, Gilfrich JJ, et al. An interaction study between benoxaprofen and digoxin. European Journal of Rheumatology and Inflammation 5: 82–86, 1982

    PubMed  CAS  Google Scholar 

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  1. Division of Clinical Pharmacology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts, 01655, USA

    Steven M. Rodin &  Brian F. Johnson

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Rodin, S.M., Johnson, B.F. Pharmacokinetic Interactions with Digoxin. Clin-Pharmacokinet 15, 227–244 (1988). https://doi.org/10.2165/00003088-198815040-00003

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