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Clinical Pharmacokinetics of Disopyramide

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Summary

Disopyramide is an antiarrhythmic agent with proven efficacy in the management of atrial and ventricular arrhythmias. The drug is well absorbed and undergoes virtually no first-pass metabolism. Peak concentrations are achieved approximately 0.5 to 3.0 hours after a dose. Absorption is reduced and slightly slowed in patients with acute myocardial infarction. Disopyramide is excreted as unchanged drug (two-thirds) or as the metabolite mono-N-desisopropyldisopyramide, with elimination via both renal and biliary routes. Elimination half-life is approximately 7 hours in normal subjects and patients, but is prolonged in patients with renal insufficiency (creatinine clearance < 60 ml/min).

Disopyramide exhibits complex protein binding. It is bound to α1-acid glycoprotein (AAG), an acute phase reactant, and binds in a concentration-dependent (saturable) manner. The unbound fraction is reduced in the presence of elevated concentrations of AAG, as are found in acute myocardial infarction and in some chronic haemodialysis patients and renal transplant recipients. Free disopyramide concentrations are low relative to total concentration in these patients. Because the pharmacological effects of disopyramide are determined by unbound drug, changes in the unbound fraction could make total disopyramide concentrations misleading as a guide to therapy. Changes in protein binding do not, however, alter free disopyramide or metabolite concentrations, both of which are dependent only on dosage and intrinsic clearance. Free drug concentration measurement could potentially improve therapeutic monitoring, but is as yet of unproven clinical value.

Disopyramide is cleared more rapidly in children than in adults, and therefore children require higher dosages to attain therapeutic concentrations.

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References

  • Aitio M. Plasma concentrations and protein binding of disopyramide and mono-N-dealkyldisopyramide during chronic oral disopyramide therapy. British Journal of Clinical Pharmacology 11: 369, 1981

    Article  PubMed  CAS  Google Scholar 

  • Aitio M, Mansury L, Tala E, Haataja M, Aitio A. The effect of enzyme induction on the metabolism of disopyramide in man. British Journal of Clinical Pharmacology 11: 279, 1981

    Article  PubMed  CAS  Google Scholar 

  • Aitio M, Virtanen R, Lammintausta R. Disopyramide concentrations in saliva. International Journal of Clinical Pharmacology, Therapeutics and Toxicology 20: 68, 1982

    CAS  Google Scholar 

  • Aitio M, Vuorenmaa T. Enhanced metabolism and diminished efficacy of disopyramide by enzyme induction? British Journal of Clinical Pharmacology 9: 149, 1980

    Article  PubMed  CAS  Google Scholar 

  • Amman K, Graffner C, Rikner L, Ryden L, Voog L. Plasma concentration of disopyramide given as capsules and controlled release tablets. European Journal of Clinical Pharmacology 24: 199, 1983

    Article  Google Scholar 

  • Baines MW, Davies JE, Kellett DN, Munt PI. Some pharmacological effects of disopyramide and a metabolite. Journal of International Medical Research 4 (Suppl.): 5, 1976

    PubMed  CAS  Google Scholar 

  • Bredesen JE, Kierulf P. Relationship between alpha-1-acid glycoprotein and plasma binding of disopyramide and mono-N-dealkyldisopyramide. British Journal of Clinical Pharmacology 18: 779, 1984

    Article  PubMed  CAS  Google Scholar 

  • Bredesen JE, Pike E, Lunde PKM. Plasma binding of disopyramide and mono-N-dealkyldisopyramide. British Journal of Clinical Pharmacology 14: 673, 1982

    Article  PubMed  CAS  Google Scholar 

  • Bryson SM, Cairns CJ, Whiting B. Disopyramide pharmacokinetics during recovery from myocardial infarction. British Journal of Clinical Pharmacology 13: 417, 1982a

    Article  PubMed  CAS  Google Scholar 

  • Bryson SM, Lawrence JR, Steele WH, Campbell BC, Elliott HL, et al. The influence of protein binding on disopyramide clearance. European Journal of Clinical Pharmacology 23: 453, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Bryson SM, Whiting B, Lawrence JR. Disopyramide serum and pharmacologic effect kinetics applied to the assessment of bioavailability. British Journal of Clinical Pharmacology 6: 409, 1978

    Article  PubMed  CAS  Google Scholar 

  • Burk M, Peters U. Disopyramide kinetics in renal impairment: determinants of interindividual variability. Clinical Pharmacology and Therapeutics 34: 331, 1983

    Article  PubMed  CAS  Google Scholar 

  • Chien YW, Lambert HJ, Karim A. Comparative binding of disopyramide phosphate and quinidine sulfate to human plasma proteins. Journal of Pharmaceutical Sciences 63: 1877, 1974

    Article  PubMed  CAS  Google Scholar 

  • Cook CS, Karim A, Soliman P. Stereoselectivity in the metabolism of disopyramide enantiomers in rat and dog. Drug Metabolism and Disposition 10: 116, 1982

    PubMed  CAS  Google Scholar 

  • Davis BM, Madsen BW, Ilett KF. Plasma binding of disopyramide. Correspondence. British Journal of Clinical Pharmacology 9: 614, 1980

    Article  Google Scholar 

  • David BM, Tjokrosetio R, Ilett KF. Plasma protein binding of disopyramide by equilibrium dialysis and ultrafiltration. Therapeutic Drug Monitoring 5: 81, 1983

    Article  PubMed  CAS  Google Scholar 

  • Dubetz DK, Brown NN, Hooper WD, Eadie MJ, Tyrer JH. Disopyramide pharmacokinetics and bioavailability. Correspondence. British Journal of Clinical Pharmacology 6: 279, 1978

    Article  PubMed  CAS  Google Scholar 

  • Duchateau AMJA, Merkus FWHM, Wilming R. Biopharmaceutical and pharmacokinetic aspects of disopyramide. Pharmaceutische Weekblad 112: 145, 1977

    CAS  Google Scholar 

  • Forssell G, Graffner C, Nordlander R, Nyguist O. Comparatiave bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets. European Journal of Clinical Pharmacology 17: 209, 1980

    Article  PubMed  CAS  Google Scholar 

  • Francois B, Mallein R, Rondelet J, Lussignol M. Pharmacokinetics of disopyramide in patients with chronic renal failure. European Journal of Drug Metabolism and Pharmacokinetics 8: 85, 1983

    Article  PubMed  CAS  Google Scholar 

  • Giacomini KM, Giacomini JC, Swezey SE, Harrison DC, Nelson WL, et al. The stereoselective disposition of disopyramide in the dog. Journal of Cardiovascular Pharmacology 2: 825, 1980

    Article  PubMed  CAS  Google Scholar 

  • Giacomini KM, Swezey SE, Turner-Tamiyasu K, Blaschke TF. The effect of saturable binding to plasma proteins on the pharmacokinetic properties of disopyramide. Journal of Pharmacokinetics and Biopharmaceutics 10: 1, 1982

    PubMed  CAS  Google Scholar 

  • Gosselin B, Mathieu D, Chopin C, Wattel F, Dupuis B, et al. Acute intoxication with diisopyramide: clinical and experimental study by hemoperfuson on Amberlite XAD 4 resin. Clinical Toxicology 17: 439, 1980

    Article  PubMed  CAS  Google Scholar 

  • Grant AM, Marshall RJ, Ankier SI. Some effects of disopyramide and its N-dealkylated metabolite on isolated nerve and cardiac muscle. European Journal of Pharmacology 49: 389, 1978

    Article  PubMed  CAS  Google Scholar 

  • Haughey DB, Kraft CJ, Matzke GR, Keane WF, Halstenson CE. Protein binding of disopyramide and elevated alpha-1-acid glycoprotein concentrations in serum obtained from dialysis patients and renal transplant recipients. American Journal of Nephrology 5: 35, 1985

    Article  PubMed  CAS  Google Scholar 

  • Haughey DB, Lima JJ. Influence of concentration-dependent protein binding on serum concentrations and urinary excretion of disopyramide and its metabolite following oral administration. Biopharmaceutics and Drug Disposition 4: 103, 1983

    Article  CAS  Google Scholar 

  • Hinderling PH, Bres J, Garrett ER. Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite. Journal of Pharmaceutical Sciences 63: 1684, 1974

    Article  PubMed  CAS  Google Scholar 

  • Hinderling PH, Garrett ER. Pharmacokinetics of the antiarrhythmic disopyramide in healthy humans. Journal of Pharmacokinetics and Biopharmaceutics 4: 199, 1976a

    PubMed  CAS  Google Scholar 

  • Hinderling PH, Garrett ER. Pharmacodynamics of the antiarrhythmic disopyramide: correlation of the kinetics of the drug and its effects. Journal of Pharmacokinetics and Biopharmaceutics 4: 231, 1976b

    PubMed  CAS  Google Scholar 

  • Holt DW, Hayler AM, Healey GF. Effect of age and plasma concentrations of albumin and alpha-1-acid glycoprotein on protein binding of disopyramide. Correspondence. British Journal of Clinical Pharmacology 16: 344, 1983

    Article  PubMed  CAS  Google Scholar 

  • Holt D, Walsh AC, Curry PVL, Tynan M. Paediatric use of mexiletine and disopyramide. British Medical Journal 2: 1476, 1979

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Øie S. Effect of altered disopyramide binding on its pharmacologic response in rabbits. Journal of Pharmacology and Experimental Therapeutics 233: 469, 1982

    Google Scholar 

  • Ilett KF, Madsen BW, Woods JD. Disopyramide kinetics in patients with acute myocardial infarction. Clinical Pharmacology and Therapeutics 27: 1, 1979

    Google Scholar 

  • Johnston A, Henry JA, Warrington, SJ, Hamer NAJ. Pharmacokinetics of oral disopyramide phosphate in patients with renal impairment. British Journal of Clinical Pharmacology 10: 245, 1980

    Article  PubMed  CAS  Google Scholar 

  • Jounela AJ, Pentikainen PJ, Oksanen K. The pharmacokinetics of disopyramide in patients with acute myocardial infarction. International Journal of Clinical Pharmacology, Therapy and Toxicology 20: 276, 1982

    CAS  Google Scholar 

  • Karim A. The pharmacokinetics of Norpace. Angiology 26 (Suppl. 1): 85, 1975

    PubMed  CAS  Google Scholar 

  • Karim A, Kook C, Campion J. Placental and milk transfer of disopyramide and metabolites. Drug Metabolism and Disposition 6: 346, 1978

    PubMed  CAS  Google Scholar 

  • Karim A, Ranney RE, Kraychy S. Species differences in the biotransformation of a new antiarrhythmic agent: disopyramide phosphate. Journal of Pharmaceutical Sciences 61: 881, 1972

    Article  Google Scholar 

  • Kumana CR, Rambihar VS, Willis K, Gupta RN, Tanser PH, et al. Absorption and antidysrhythmic activity of oral disopyramide phosphate after acute myocardial infarction. British Journal of Clinical Pharmacology 14: 529, 1982

    Article  PubMed  CAS  Google Scholar 

  • Landmark K, Bredesen JE, Thaulow E, Simonsen S, Amlie JP. Pharmacokinetics of disopyramide in patients with imminent to moderate cardiac failure. European Journal of Clinical Pharmacology 19: 187, 1981

    Article  PubMed  CAS  Google Scholar 

  • Liem KL, Hollander JMR. Maintenance therapy after i.v. administration of disopyramide with an oral sustained release preparation, a pharmacokinetic study. British Journal of Clinical Pharmacology 18: 226, 1984

    Article  PubMed  CAS  Google Scholar 

  • Lima JJ, Haughey DB. Disopyramide binding to serum protein in man and animals. Drug Metabolism and Disposition 9: 582, 1981

    PubMed  CAS  Google Scholar 

  • Lima JJ, Haughey DB, Leier CV. Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and 14C-disopyramide. Journal of Pharmacokinetics and Biopharmaceutics 12: 289, 1984a

    PubMed  CAS  Google Scholar 

  • Lima JJ, Jungbluth GL, Devine T, Robertson LW. Stereoselective binding of disopyramide to human plasma protein. Life Sciences 35: 835, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Meffin PJ, Robert EW, Winkle RA, Harapat S, Peters, FA, et al. Role of concentration-dependent plasma protein binding in disopyramide disposition. Journal of Pharmacokinetics and Biopharmaceutics 7: 29, 1979

    PubMed  CAS  Google Scholar 

  • Niarchos AP. Disopyramide: serum levels and arrhythmia conversion. American Heart Journal 92: 57, 1976

    Article  PubMed  CAS  Google Scholar 

  • Olsen H, Bredesen JE, Lunde PKM. Effect of ethanol intake on disopyramide elimination by healthy volunteers. European Journal of Clinical Pharmacology 25: 103, 1983

    Article  PubMed  CAS  Google Scholar 

  • Patterson E, Stetson P, Lucchesi BR. Disopyramide plasma and myocardial tissue concentrations as they relate to antiarrhythmic activity. American Journal of Cardiology 43: 358, 1979

    Google Scholar 

  • Piafsky KM, Sellers EM, Strauss H, Woolner B. Plasma binding of lidocaine, disopyramide and propranolol in acute myocardial infarction. In Turner P. & Padgham C. (Eds) World Conference on Clinical Pharmacology and Therapeutics, Abstract 0346, MacMillan, London, 1980

    Google Scholar 

  • Pollick C, Giacomini KM, Blaschke TF, Nelson WL, Turner-Tamiyasu K, et al. The cardiac effects of d- and 1-disopyramide in normal subjects: a noninvasive study. Circulation 66: 447, 1982

    Article  PubMed  CAS  Google Scholar 

  • Rangno RE, Warnica W, Ogilvie RI, Kreeft J, Bridger E. Correlation of disopyramide pharmacokinetics with efficacy in ventricular tachyarrhythmia. Journal of International Medical Research 4 (Suppl. 1): 54, 1976

    PubMed  CAS  Google Scholar 

  • Sevka MJ, Matthews SJ, Nightingale CH, Izard MW, Fieldman A, et al. Disopyramide hemodialysis and kinetics in patients requiring long-term hemodialysis. Clinical Pharmacology and Therapeutics 29: 322, 1981

    Article  PubMed  CAS  Google Scholar 

  • Shaxted EJ, Milton PJ. Disopyramide in pregnancy: a case report. Current Medical Research and Opinion 6: 70, 1979

    Article  PubMed  CAS  Google Scholar 

  • Tynan M, Keaton BR, Hayler AM, Holt D. The dosage of disopyramide in infants and children. British Journal of Clinical Practice Symposia 11 (Suppl.): 40, 1981

    Google Scholar 

  • Ward JW, Kinghorn GR. The pharmacokinetics of disopyramide following myocardial infarction with special reference to oral and intravenous dose regimens. Journal of International Medical Research 4 (Suppl. 1): 49, 1976

    PubMed  CAS  Google Scholar 

  • Weissberg PL, Matenga J, Hayler AM, Holt DW. Plasma disopyramide concentrations following a 300-mg oral loading dose in acute myocardial infarction. Therapeutic Drug Monitoring 4: 277, 1982

    Article  PubMed  CAS  Google Scholar 

  • Whiting B, Holford NHG, Sheiner LB. Quantitative analysis of the disopyramide concentration-effect relationship. British Journal of Clinical Pharmacology 9: 67, 1980

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, USA

    Lyle A. Siddoway &  Raymond L. Woosley

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  1. Lyle A. Siddoway
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  2. Raymond L. Woosley
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Siddoway, L.A., Woosley, R.L. Clinical Pharmacokinetics of Disopyramide. Clin-Pharmacokinet 11, 214–222 (1986). https://doi.org/10.2165/00003088-198611030-00003

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