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Therapeutic Drug Monitoring of Antiarrhythmic Drugs

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Abstract

Most antiarrhythmic drugs fulfil the formal requirements for rational use of therapeutic drug monitoring, as they show highly variable plasma concentration profiles at a given dose and a direct concentration-effect relationship. Therapeutic ranges for antiarrhythmic drugs are, however, often very poorly defined. Effective drug concentrations are based on small studies or studies not designed to establish a therapeutic range, with varying dosage regimens and unstandardised sampling procedures. There are large numbers of nonresponders and considerable overlap between therapeutic and toxic concentrations. Furthermore, no study has ever shown that therapeutic drug monitoring makes a significant difference in clinical outcome.

Therapeutic concentration ranges for antiarrhythmic drugs as they exist today can give an overall impression about the drug concentrations required in the majority of patients. They may also be helpful for dosage adjustment in patients with renal or hepatic failure or in patients with possible toxicological or compliance problems. Their use in optimising individual antiarrhythmic therapy, however, is very limited.

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References

  1. Jannuzzi G, Cian P, Fattore C, et al. A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy. Epilepsia 2000 Feb; 41(2): 222–30

    Article  PubMed  CAS  Google Scholar 

  2. Kemme DJ, Daniel CI. Aminoglycoside dosing: a randomized prospective study. South Med J 1993 Jan; 86(1): 46–51

    Article  PubMed  CAS  Google Scholar 

  3. Jelliffe RW, Schumitzky A, Bayard D, et al. Model-based, goaloriented, individualised drug therapy: linkage of population modelling, new ‘multiple model’ dosage design, Bayesian feedback and individualised target goals. Clin Pharmacokinet 1998 Jan; 34(1): 57–77

    Article  PubMed  CAS  Google Scholar 

  4. Gross AS, Mikus G, Fischer C, et al. Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype. Br J Clin Pharmacol 1989 Nov; 28(5): 555–66

    Article  PubMed  CAS  Google Scholar 

  5. Labbe L, Turgeon J. Clinical pharmacokinetics of mexiletine. Clin Pharmacokinet 1999 Nov; 37(5): 361–84

    Article  PubMed  CAS  Google Scholar 

  6. Giacomini KM, Cox BM, Blaschke TF. Comparative anticholinergic potencies. Life Sci 1980 Sep; 27(13): 1191–7

    Article  PubMed  CAS  Google Scholar 

  7. Lima JJ, Boudoulas H. Stereoselective effects of disopyramide enantiomers in humans. J Cardiovasc Pharmacol 1987 May; 9(5): 594–600

    Article  PubMed  CAS  Google Scholar 

  8. Eichelbaum M, Mikus G, Vogelgesang B. Pharmacokinetics of (+)-, (−)- and (±)-verapamil after intravenous administration. Br J Clin Pharmacol 1984 Apr; 17(4): 453–8

    Article  PubMed  CAS  Google Scholar 

  9. Burgess CD, Siebers RW, Purdie GL, et al. The relationship between the QT interval and plasma amiodarone concentration in patients on long-term therapy. Eur J Clin Pharmacol 1987; 33(2): 115–8

    Article  PubMed  CAS  Google Scholar 

  10. Roden DM, Reele SB, Higgins SB, et al. Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: comparison with procainamide. Am J Cardiol 1980 Sep; 46(3): 463–8

    Article  PubMed  CAS  Google Scholar 

  11. Aitio ML, Vuorenmaa T. Enhanced metabolism and diminished efficacy of disopyramide by enzyme induction? Br J Clin Pharmacol 1980 Feb; 9(2): 149–52

    Article  PubMed  CAS  Google Scholar 

  12. David BM, Ilett KF, Whitford EG, et al. Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction. Br J Clin Pharmacol 1983 Apr; 15(4): 435–41

    Article  PubMed  CAS  Google Scholar 

  13. Caplin JL, Johnston A, Hamer J, et al. The acute changes in serum binding of disopyramide and flecainide after myocardial infarction. Eur J Clin Pharmacol 1985; 28(3): 253–5

    Article  PubMed  CAS  Google Scholar 

  14. Routledge PA, Shand DG, Barchowsky A, et al. Relationship between alpha 1-acid glycoprotein and lidocaine disposition in myocardial infarction. Clin Pharmacol Ther 1981 Aug; 30(2): 154–7

    Article  PubMed  CAS  Google Scholar 

  15. Routledge PA, Stargel WW, Wagner GS, et al. Increased alpha-1-acid glycoprotein and lidocaine disposition in myocardial infarction. Ann Intern Med 1980 Nov; 93(5): 701–4

    PubMed  CAS  Google Scholar 

  16. McCollam PL, Crouch MA, Watson JE. Altered protein binding of quinidine in patients with atrial fibrillation and flutter. Pharmacotherapy 1997 Jul; 17(4): 753–9

    PubMed  CAS  Google Scholar 

  17. Ha HR, Vozeh S, Uematsu T, et al. Kinetics and dynamics of quinidine-N-oxide in healthy subjects. Clin Pharmacol Ther 1987 Sep; 42(3): 341–5

    Article  PubMed  CAS  Google Scholar 

  18. Gerhardt RE, Knouss RF, Thyrum PT, et al. Quinidine excretion in aciduria and alkaluria. Ann Intern Med 1969 Nov; 71(5): 927–33

    PubMed  CAS  Google Scholar 

  19. Mahon WA, Mayersohn M, Inaba T. Disposition kinetics of two oral forms of quinidine. Clin Pharmacol Ther 1976 May; 19 (5 Pt 1): 566–75

    PubMed  CAS  Google Scholar 

  20. Mihaly GW, Ching MS, Klejn MB, et al. Differences in the binding of quinine and quinidine to plasma proteins. Br J Clin Pharmacol 1987 Dec; 24(6): 769–74

    Article  PubMed  CAS  Google Scholar 

  21. Ueda CT, Hirschfeld DS, Scheinman MM, et al. Disposition kinetics of quinidine. Clin Pharmacol Ther 1976 Jan; 19(1): 30–6

    PubMed  CAS  Google Scholar 

  22. Niarchos AP. Disopyramide: serum level and arrhythmia conversion. Am Heart J 1976 Jul; 92(1): 57–64

    Article  PubMed  CAS  Google Scholar 

  23. Hore P, Bones P, Rollinson T, et al. A pharmacokinetic comparison of two sustained-release oral procainamide preparations. Br J Clin Pharmacol 1979 Sep; 8(3): 267–71

    Article  PubMed  CAS  Google Scholar 

  24. Dreyfuss J, Bigger Jr JT, Cohen AI, et al. Metabolism of procainamide in rhesus monkey and man. Clin Pharmacol Ther 1972 May; 13(3): 366–71

    PubMed  CAS  Google Scholar 

  25. Giardina EG, Dreyfuss J, Bigger Jr JT, et al. Metabolism of procainamide in normal and cardiac subjects. Clin Pharmacol Ther 1976 Mar; 19(3): 339–51

    PubMed  CAS  Google Scholar 

  26. Koch-Weser J. Pharmacokinetic of procainamide in man. Ann N Y Acad Sci 1971 Jul; 179: 370–82

    Article  PubMed  CAS  Google Scholar 

  27. Verbesselt R, Tjandramaga TB, De Schepper PJ. High-performance liquid Chromatographie determination of 12 antiarrhythmic drugs in plasma using solid-phase column extraction. Ther Drug Monit 1991 Mar; 13(2): 157–65

    Article  PubMed  CAS  Google Scholar 

  28. Morady F, Scheinman MM, Desai J. Disopyramide. Ann Intern Med 1982 Mar; 96(3): 337–43

    PubMed  CAS  Google Scholar 

  29. Hinderling PH, Garrett ER. Pharmacodynamics of the antiarrhythmic disopyramide in healthy humans: correlation of the kinetics of the drug and its effects. J Pharmacokinet Biopharm 1976 Jun; 4(3): 231–42

    Article  PubMed  CAS  Google Scholar 

  30. Siddoway LA, Woosley RL. Clinical pharmacokinetics of disopyramide. Clin Pharmacokinet 1986 May; 11(3): 214–22

    Article  PubMed  CAS  Google Scholar 

  31. Grant AM, Marshall RJ, Ankier S. I. Some effects of disopyramide and its N-dealkylated metabolite on isolated nerve and cardiac muscle. Eur J Pharmacol 1978 Jun; 49(4): 389–94

    Article  PubMed  CAS  Google Scholar 

  32. Baines MW, Davies JE, Kellett DN, et al. Some pharmacological effects of disopyramide and a metabolite. J Int Med Res 1976; 4 (1 Suppl.): 5–7

    PubMed  CAS  Google Scholar 

  33. Zito RA, Reid PR. Lidocaine kinetics: relationships between early lidocaine kinetics and indocyanine green clearance. J Clin Pharmacol 1981 Feb; 21(2): 100–5

    PubMed  CAS  Google Scholar 

  34. Elvin AT, Cole AF, Pieper JA, et al. Effect of food on lidocaine kinetics: mechanism of food-related alteration in high intrinsic clearance drug elimination. Clin Pharmacol Ther 1981 Oct; 30(4): 455–60

    Article  PubMed  CAS  Google Scholar 

  35. Boyes RN, Scott DB, Jebson PJ, et al. Pharmacokinetics of lidocaine in man. Clin Pharmacol Ther 1971 Jan; 12(1): 105–16

    PubMed  CAS  Google Scholar 

  36. Eriksson E. Prilocaine: an experimental study in man of a new local anaesthetic with special regards to efficacy, toxicity and excretion. Acta Chir Scand Suppl 1966; 358: 1–82

    PubMed  CAS  Google Scholar 

  37. Thomson PD, Melmon KL, Richardson JA, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 1973 Apr; 78(4): 499–508

    PubMed  CAS  Google Scholar 

  38. Prescott LF, Pottage A, Clements JA. Absorption, distribution and elimination of mexiletine. Postgrad Med J 1977; 53 Suppl. 1: 50–5

    PubMed  CAS  Google Scholar 

  39. Beckett AH, Chidomere EC. The distribution, metabolism and excretion of mexiletine in man. Postgrad Med J 1977; 53 Suppl. 1: 60–8

    PubMed  CAS  Google Scholar 

  40. Haselbarth V, Doevendans JE, Wolf M. Kinetics and bioavailability of mexiletine in healthy subjects. Clin Pharmacol Ther 1981 Jun; 29(6): 729–36

    Article  PubMed  CAS  Google Scholar 

  41. Conard GJ, Ober RE. Metabolism of flecainide. Am J Cardiol 1984 Feb; 53(5): 41B–51B

    Article  PubMed  CAS  Google Scholar 

  42. Tjandra-Maga TB, Verbesselt R, Van Hecken A, et al. Flecainide: single and multiple oral dose kinetics, absolute bioavailability and effect of food and antacid in man. Br J Clin Pharmacol 1986 Sep; 22(3): 309–16

    Article  PubMed  CAS  Google Scholar 

  43. Conard GJ, Carlson GL, Frost JW, et al. Plasma concentrations of flecainide acetate, a new antiarrhythmic agent, in humans. Clin Ther 1984; 6(5): 643–52

    PubMed  CAS  Google Scholar 

  44. Connolly SJ, Kates RE, Lebsack CS, et al. Clinical pharmacology of Propafenone. Circulation 1983 Sep; 68(3): 589–96

    Article  PubMed  CAS  Google Scholar 

  45. Hollmann M, Brode E, Hotz D, et al. Investigations on the pharmacokinetics of Propafenone in man. Arzneimittel Forschung 1983; 33(5): 763–70

    PubMed  CAS  Google Scholar 

  46. Siddoway LA, Roden DM, Woosley RL. Clinical pharmacology of Propafenone: pharmacokinetics, metabolism and concentration-response relations. Am J Cardiol 1984 Nov; 54(9): 9D–12D

    Article  PubMed  CAS  Google Scholar 

  47. Gillis AM, Yee YG, Kates RE. Binding of antiarrhythmic drags to purified human alpha 1-acid glycoprotein. Biochem Pharmacol 1985 Dec; 34(24): 4279–82

    Article  PubMed  CAS  Google Scholar 

  48. Andreasen F, Agerbaek H, Bjerregaard P, et al. Pharmacokinetics of amiodarone after intravenous and oral administration. Eur J Clin Pharmacol 1981 Mar; 19(4): 293–9

    Article  PubMed  CAS  Google Scholar 

  49. Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet 1984 Mar; 9(2): 136–56

    Article  PubMed  CAS  Google Scholar 

  50. Naccarelli GV, Rinkenberger RL, Dougherty AH, et al. Amiodarone: pharmacology and antiarrhythmic and adverse effects. Pharmacotherapy 1985 Nov; 5(6): 298–313

    PubMed  CAS  Google Scholar 

  51. Anttila M, Arstila M, Pfeffer M, et al. Human pharmacokinetics of Sotalol. Acta Pharmacol Toxicol (Copenh) 1976 Jul; 39(1): 118–28

    Article  CAS  Google Scholar 

  52. Uematsu T, Kanamaru M, Nakashima M. Comparative pharmacokinetic and pharmacodynamic properties of oral and intravenous (+)-sotalol in healthy volunteers. J Pharm Pharmacol 1994 Jul; 46(7): 600–5

    Article  PubMed  CAS  Google Scholar 

  53. Sundquist H, Anttila M, Simon A, et al. Comparative bioavailability and pharmacokinetics of sotalol administered alone and in combination with hydrochlorothiazide. J Clin Pharmacol 1979 Aug; 19 (8–9 Pt 2): 557–64

    PubMed  CAS  Google Scholar 

  54. Sotaniemi EA, Anttila M, Pelkonen RO, et al. Plasma clearance of Propranolol and sotalol and hepatic drug- metabolizing enzyme activity. Clin Pharmacol Ther 1979 Aug; 26(2): 153–61

    PubMed  CAS  Google Scholar 

  55. Anderson JL, Prystowsky EN. Sotalol: an important new antiarrhythmic. Am Heart J 1999 Mar; 137(3): 388–409

    Article  PubMed  CAS  Google Scholar 

  56. Hui J, Wang YM, Chandrasekaran A, et al. Disposition of tablet and capsule formulations of digoxin in the elderly. Pharmacotherapy 1994 Sep; 14(5): 607–12

    PubMed  CAS  Google Scholar 

  57. Mooradian AD. Digitalis: an update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations. Clin Pharmacokinet 1988 Sep; 15(3): 165–79

    Article  PubMed  CAS  Google Scholar 

  58. Ochs HR, Bodem G, Greenblatt DJ. Effect of dose on bioavailability of oral digoxin. Eur J Clin Pharmacol 1981 Jan; 19(1): 53–5

    Article  PubMed  CAS  Google Scholar 

  59. Hinderling PH, Bres J, Garrett ER. Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite. J Pharm Sci 1974 Nov; 63(11): 1684–90

    Article  PubMed  CAS  Google Scholar 

  60. Meffin PJ, Robert EW, Winkle RA, et al. Role of concentrationdependent plasma protein binding in disopyramide disposition. J Pharmacokinet Biopharm 1979 Feb; 7(1): 29–46

    Article  PubMed  CAS  Google Scholar 

  61. Friedman PL, Stevenson WG. Proarrhythmia. Am J Cardiol 1998 Oct; 82(8A): 50N–8N

    Article  PubMed  CAS  Google Scholar 

  62. Horowitz LN, Zipes DP, Bigger Jr JT, et al. Proarrhythmia, arrhythmogenesis or aggravation of arrhythmia: a status report, 1987. Am J Cardiol 1987 Apr; 59(11): 54E–6E

    Article  PubMed  CAS  Google Scholar 

  63. Caron J, Libersa C. Adverse effects of class I antiarrhythmic drugs. Drag Saf 1997 Jul; 17(1): 8–36

    Article  CAS  Google Scholar 

  64. Campbell TJ, Williams KM. Therapeutic drag monitoring: antiarrhythmic drags. Br J Clin Pharmacol 1998 Oct; 46(4): 307–19

    Article  PubMed  CAS  Google Scholar 

  65. Jackman WM, Friday KJ, Anderson JL, et al. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988 Sep; 31(2): 115–72

    Article  PubMed  CAS  Google Scholar 

  66. Roden DM, Hoffman BF. Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers: relationship to potassium and cycle length. Circ Res 1985 Jun; 56(6): 857–67

    Article  PubMed  CAS  Google Scholar 

  67. Roden DM, Thompson KA, Hoffman BF, et al. Clinical features and basic mechanisms of quinidine-induced arrhythmias. J Am Coll Cardiol 1986 Jul; 8 (1 Suppl. A): 73A–8A

    Article  PubMed  CAS  Google Scholar 

  68. Roden DM. Mechanisms and management of proarrhythmia. Am J Cardiol 1998 Aug; 82(4A): 491–571

    Google Scholar 

  69. Wyse KR, Ye V, Campbell TJ. Action potential prolongation exhibits simple dose-dependence for sotalol, but reverse dose-dependence for quinidine and disopyramide: implications for proarrhythmia due to triggered activity. J Cardiovasc Pharmacol 1993 Feb; 21(2): 316–22

    Article  PubMed  CAS  Google Scholar 

  70. Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of Sotalol in patients with arrhythmias. Am J Cardiol 1990 Jan; 65(2): 74A–81A

    Article  PubMed  CAS  Google Scholar 

  71. Hohnloser SH, Singh BN. Proarrhythmia with class III antiarrhythmic drags: definition, electrophysiologic mechanisms, incidence, predisposing factors, and clinical implications. J Cardiovasc Electrophysiol 1995 Oct; 6 (10 Pt 2): 920–36

    Article  PubMed  CAS  Google Scholar 

  72. Kerin NZ, Somberg J. Proarrhythmia: definition, risk factors, causes, treatment, and controversies. Am Heart J 1994 Sep; 128(3): 575–85

    Article  PubMed  CAS  Google Scholar 

  73. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991 Mar; 324(12): 781–8

    Article  PubMed  CAS  Google Scholar 

  74. Galloe A, Graudal N. Magnesium and myocardial infarction. Lancet 1994 May; 343(8908): 1286–7

    PubMed  CAS  Google Scholar 

  75. Koch-Weser J, Klein SW. Procainamide dosage schedules, plasma concentrations, and clinical effects. JAMA 1971 Mar; 215(9): 1454–60

    Article  PubMed  CAS  Google Scholar 

  76. Young JB, Gheorghiade M, Packer M, et al. Are low serum levels of digoxin effective in chronic heart failure [abstract]? J Am Coll Cardiol 1993; 21: 378A

    Google Scholar 

  77. Rakhit A, Holford NH, Guentert TW, et al. Pharmacokinetics of quinidine and three of its metabolites in man. J Pharmacokinet Biopharm 1984 Feb; 12(1): 1–21

    Article  PubMed  CAS  Google Scholar 

  78. Greenblatt DJ, Pfeifer HJ, Ochs HR, et al. Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration. J Pharmacol Exp Ther 1977 Aug; 202(2): 365–78

    PubMed  CAS  Google Scholar 

  79. Sokolow M, Ball RE. Factors influencing conversion of chronic atrial fibrillation with special reference to serum quinidine concentration. Circulation 1956; 14: 568–83

    Article  PubMed  Google Scholar 

  80. Vozeh S, Uematsu T, Guentert TW, et al. Kinetics and electro-cardiographic changes after oral 3-OH-quinidine in healthy subjects. Clin Pharmacol Ther 1985 May; 37(5): 575–81

    Article  PubMed  CAS  Google Scholar 

  81. Drayer DE, Lowenthal DT, Restivo KM, et al. Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. Clin Pharmacol Ther 1978 Jul; 24(1): 31–9

    PubMed  CAS  Google Scholar 

  82. Chimienti M, Regazzi MB, La Rovere MT, et al. Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration. Cardiovasc Drugs Ther 1988 Dec; 2(5): 679–86

    Article  PubMed  CAS  Google Scholar 

  83. Vozeh S, Bindschedler M, Ha HR, et al. Pharmacodynamics of 3-hydroxyquinidine alone and in combination with quinidine in healthy persons. Am J Cardiol 1987 Mar; 59(6): 681–4

    Article  PubMed  CAS  Google Scholar 

  84. Verme CN, Ludden TM, Clementi WA, et al. Pharmacokinetics of quinidine in male patients: a population analysis. Clin Pharmacokinet 1992 Jun; 22(6): 468–80

    Article  PubMed  CAS  Google Scholar 

  85. Carliner NH, Fisher ML, Crouthamel WG, et al. Relation of ventricular premature beat suppression to serum quinidine concentration determined by a new and specific assay. Am Heart J 1980 Oct; 100(4): 483–9

    Article  PubMed  CAS  Google Scholar 

  86. Sami M, Harrison DC, Kraemer H, et al. Antiarrhythmic efficacy of encainide and quinidine: validation of a model for drag assessment. Am J Cardiol 1981 Jul; 48(1): 147–56

    Article  PubMed  CAS  Google Scholar 

  87. Follath F, Ganzinger U, Schuetz E. Reliability of antiarrhythmic drug plasma concentration monitoring. Clin Pharmacokinet 1983 Jan; 8(1): 63–82

    Article  PubMed  CAS  Google Scholar 

  88. Latini R, Maggioni AP, Cavalli A. Therapeutic drag monitoring of antiarrhythmic drugs: rationale and current status. Clin Pharmacokinet 1990 Feb; 18(2): 91–103

    Article  PubMed  CAS  Google Scholar 

  89. Valdes Jr R, Jortani SA, Gheorghiade M. Standards of laboratory practice: cardiac drug monitoring. National Academy of Clinical Biochemistry. Clin Chem 1998 May; 44(5): 1096–109

    PubMed  CAS  Google Scholar 

  90. Elson J, Strong JM, Lee WK, et al. Antiarrhythmic potency of N-acetylprocainamide. Clin Pharmacol Ther 1975 Feb; 17(2): 134–40

    PubMed  CAS  Google Scholar 

  91. Reidenberg MM, Drayer DE, Levy M, et al. Polymorphic acetylation of procainamide in man. Clin Pharmacol Ther 1975 Jun; 17(6): 722–30

    PubMed  CAS  Google Scholar 

  92. Drayer DE, Reidenberg MM. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther 1977 Sep; 22(3): 251–8

    PubMed  CAS  Google Scholar 

  93. Tilstone WJ, Lawson DH, Campbell W, et al. The pharmacokinetics of slow-release procainamide. Eur J Clin Pharmacol 1978 Dec; 14(4): 261–5

    Article  PubMed  CAS  Google Scholar 

  94. Giardina EG, Heissenbuttel RH, Bigger Jr JT. Intermittent intravenous procaine amide to treat ventricular arrhythmias. Correlation of plasma concentration with effect on arrhythmia, electrocardiogram, and blood pressure. Ann Intern Med 1973 Feb; 78(2): 183–93

    PubMed  CAS  Google Scholar 

  95. Giardina EG, Fenster PE, Bigger Jr JT, et al. Efficacy, plasma concentrations and adverse effects of a new sustained release procainamide preparation. Am J Cardiol 1980 Nov; 46(5): 855–62

    Article  PubMed  CAS  Google Scholar 

  96. Winkle RA, Jaillon P, Kates RE, et al. Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide. Am J Cardiol 1981 Jan; 47(1): 123–30

    Article  PubMed  CAS  Google Scholar 

  97. Burke Jr TR, Nelson WL, Mangion M, et al. Resolution, absolute configuration, and antiarrhythmic properties of the enantiomers of disopyramide, 4-(diisopropylamino)-2-(2-pyridyl)-2-phenylbutyramide. J Med Chem 1980 Sep; 23(9): 1044–8

    Article  PubMed  CAS  Google Scholar 

  98. Karim A. The pharmacokinetics of Norpace. Angiology 1975 Jan; 26 (1 Pt 2): 85–98

    PubMed  CAS  Google Scholar 

  99. Dreifus LS. Clinical studies of Norpace (Part X). Angiology 1975 Jan; 26 (1 Pt 2): 148

    PubMed  CAS  Google Scholar 

  100. Bonde J, Jensen NM, Pedersen LE, et al. Elimination kinetics and urinary excretion of disopyramide in human healthy volunteers. Pharmacol Toxicol 1988 May; 62(5): 298–301

    Article  PubMed  CAS  Google Scholar 

  101. Cunningham JL, Shen DD, Shudo I, et al. The effects of urine pH and plasma protein binding on the renal clearance of disopyramide. Clin Pharmacokinet 1977 Sep; 2(5): 373–83

    Article  PubMed  CAS  Google Scholar 

  102. Ranney RE, Dean RR, Karim A, et al. Disopyramide phosphate: pharmacokinetic and pharmacologic relationships of a new antiarrhythmic agent. Arch Int Pharmacodyn Ther 1971 May; 191(1): 162–88

    PubMed  CAS  Google Scholar 

  103. Whiting B, Holford NH, Sheiner LB. Quantitative analysis of the disopyramide concentration-effect relationship. Br J Clin Pharmacol 1980 Jan; 9(1): 67–75

    Article  PubMed  CAS  Google Scholar 

  104. Hulting J, Jansson B. Antiarrhythmic and electrocardiographic effects of single oral doses of disopyramide. Eur J Clin Pharmacol 1977 Jan; 11(2): 91–9

    Article  PubMed  CAS  Google Scholar 

  105. Sbarbaro JA, Rawling DA, Fozzard HA. Suppression of ventricular arrhythmias with intravenous disopyramide and lidocaine: efficacy comparison in a randomized trial. Am J Cardiol 1979 Sep; 44(3): 513–20

    Article  PubMed  CAS  Google Scholar 

  106. Kishikawa T, Maruyama T, Kaji Y, et al. Effects of oral repetitive loading of disopyramide on acute-onset atrial fibrillation with concurrent monitoring of serum drug concentration. Int J Cardiol 1999 Jan; 68(1): 57–62

    Article  PubMed  CAS  Google Scholar 

  107. Bredesen JE, Pike E, Lunde PK. Plasma binding of disopyramide and mono-N-dealkyldisopyramide. Br J Clin Pharmacol 1982 Nov; 14(5): 673–6

    Article  PubMed  CAS  Google Scholar 

  108. Piscitelli DA, Fischer JH, Schoen MD, et al. Bioavailability of total and unbound disopyramide: implications for clinical use of the immediate and controlled-release dosage forms. J Clin Pharmacol 1994 Aug; 34(8): 823–8

    PubMed  CAS  Google Scholar 

  109. Shaw LM, Doherty JU, Waxman HL, et al. The pharmacokinetic and pharmacodynamic effects of varying the free fraction of disopyramide. Angiology 1987 Feb; 38 (2 Pt 2): 192–7

    PubMed  CAS  Google Scholar 

  110. Bennett PN, Aarons LJ, Bending MR, et al. Pharmacokinetics of lidocaine and its deethylated metabolite: dose and time dependency studies in man. J Pharmacokinet Biopharm 1982 Jun; 10(3): 265–81

    Article  PubMed  CAS  Google Scholar 

  111. Stenson RE, Constantino RT, Harrison DC. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 1971 Feb; 43(2): 205–11

    Article  PubMed  CAS  Google Scholar 

  112. Collinsworth KA, Kaiman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrhythymic drug. Circulation 1974 Dec; 50(6): 1217–30

    Article  PubMed  CAS  Google Scholar 

  113. Sadowski ZP, Alexander JH, Skrabucha B, et al. Multicenter randomized trial and a systematic overview of lidocaine in acute myocardial infarction. Am Heart J 1999 May; 137(5): 792–8

    Article  PubMed  CAS  Google Scholar 

  114. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996 Nov; 28(5): 1328–428

    Article  PubMed  CAS  Google Scholar 

  115. MacMahon S, Collins R, Peto R, et al. Effects of prophylactic lidocaine in suspected acute myocardial infarction: an overview of results from the randomized, controlled trials. JAMA 1988 Oct; 260(13): 1910–6

    Article  PubMed  CAS  Google Scholar 

  116. Strong JM, Mayfield DE, Atkinson Jr AJ, et al. Pharmacological activity, metabolism, and pharmacokinetics of glycinexylidide. Clin Pharmacol Ther 1975 Feb; 17(2): 184–94

    PubMed  CAS  Google Scholar 

  117. Blumer J, Strong JM, Atkinson Jr AJ. The convulsant potency of lidocaine and its N-dealkylated metabolites. J Pharmacol Exp Ther 1973 Jul; 186(1): 31–6

    PubMed  CAS  Google Scholar 

  118. Halkin H, Meffin P, Melmon KL, et al. Influence of congestive heart failure on blood vessels of lidocaine and its active monodeethylated metabolite. Clin Pharmacol Ther 1975 Jun; 17(6): 669–76

    PubMed  CAS  Google Scholar 

  119. Sheldon R, Thakore E, Wilson L, et al. Interaction of drug metabolites with the class I antiarrhythmic drug receptor on rat cardiac myocytes. J Pharmacol Exp Ther 1994 May; 269(2): 477–81

    PubMed  CAS  Google Scholar 

  120. Jones DA, McBurney A, Stanley PJ, et al. Plasma concentrations of lignocaine and its metabolites during fibreoptic bronchoscopy. Br J Anaesth 1982 Aug; 54(8): 853–7

    Article  PubMed  CAS  Google Scholar 

  121. Gianelly R, der Groeben JO, Spivack AP, et al. Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. N Engl J Med 1967 Dec; 277(23): 1215–9

    Article  PubMed  CAS  Google Scholar 

  122. Bellet S, Roman L, Kostis JB, et al. Intramuscular lidocaine in the therapy of ventricular arrhythmias. Am J Cardiol 1971 Mar; 27(3): 291–3

    Article  PubMed  CAS  Google Scholar 

  123. Schwartz ML, Meyer MB, Covino BG, et al. Antiarrhythmic effectiveness of intramuscular lidocaine: influence of different injection sites. J Clin Pharmacol 1974 Feb; 14(2): 77–83

    PubMed  CAS  Google Scholar 

  124. Fehmers MC, Dunning AJ. Intramuscularly and orally administered lidocaine in the treatment of ventricular arrhythmias in acute myocardial infarction. Am J Cardiol 1972 Apr; 29(4): 514–9

    Article  PubMed  CAS  Google Scholar 

  125. Lie KI, Wellens HJ, van Capelle FJ, et al. Lidocaine in the prevention of primary ventricular fibrillation: a double-blind, randomized study of 212 consecutive patients. N Engl J Med 1974 Dec; 291(25): 1324–6

    Article  PubMed  CAS  Google Scholar 

  126. Mahon WA, Mayersohn M, Inaba T. Disposition kinetics of two oral forms of quinidine. Clin Pharmacol Ther 1976 May; 19 (5 Pt 1): 566–75

    PubMed  CAS  Google Scholar 

  127. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Circulation 1996 Nov; 94(9): 2341–50

    Article  PubMed  CAS  Google Scholar 

  128. Sadowski ZP, Alexander JH, Skrabucha B, et al. Multicenter randomized trial and a systematic overview of lidocaine in acute myocardial infarction. Am Heart J 1999 May; 137(5): 792–8

    Article  PubMed  CAS  Google Scholar 

  129. McComish M, Kitson D, Robinson C, et al. Clinical electrophysiological effects of mexiletine. Postgrad Med J 1977; 53 Suppl. 1: 85–91

    PubMed  Google Scholar 

  130. Shanks RG. Hemodynamic effects of mexiletine. Am Heart J 1984 May; 107 (5 Pt 2): 1065–71

    Article  PubMed  CAS  Google Scholar 

  131. Shaw TR. The effect of mexiletine on left ventricular ejection: a comparison with lignocaine and Propranolol. Postgrad Med J 1977; 53 Suppl. 1: 69–73

    Article  PubMed  CAS  Google Scholar 

  132. Yamaguchi I, Singh BN, Mandel WJ. Electrophysiological actions of mexiletine on isolated rabbit atria and canine ventricular muscle and purkinje fibres. Cardiovasc Res 1979 May; 13(5): 288–96

    Article  PubMed  CAS  Google Scholar 

  133. Brown JE, Shand DG. Therapeutic drug monitoring of antiarrhythmic agents. Clin Pharmacokinet 1982 Mar; 7(2): 125–48

    Article  PubMed  CAS  Google Scholar 

  134. Singh BN, Cho YW, Kuemmerle HP. Clinical pharmacology of antiarrhythmic drugs: a review and overview, part II. Int J Clin Pharmacol Ther Toxicol 1981 May; 19(5): 185–99

    PubMed  Google Scholar 

  135. Woosley RL, Wang T, Stone W, et al. Pharmacology, electrophysiology, and pharmacokinetics of mexiletine. Am Heart J 1984 May; 107 (5 Pt 2): 1058–65

    Article  PubMed  CAS  Google Scholar 

  136. Campbell NP, Kelly JG, Shanks RG, et al. Mexiletine (Ko 1173) in the management of ventricular dysrhythmias. Lancet 1973 Aug; II(7826): 404–7

    Article  Google Scholar 

  137. Talbot RG, Nimmo J, Julian DG, et al. Treatment of ventricular arrhythmias with mexiletine (Ko 1173). Lancet 1973 Aug; II(7826): 399–404

    Article  Google Scholar 

  138. Chew CY, Collett J, Singh BN. Mexiletine: a review of its pharmacological properties and therapeutic efficacy in arrhythmias. Drugs 1979 Mar; 17(3): 161–81

    Article  PubMed  CAS  Google Scholar 

  139. Campbell NP, Kelly JG, Adgey AA, et al. The clinical pharmacology of mexiletine. Br J Clin Pharmacol 1978 Aug; 6(2): 103–8

    Article  PubMed  CAS  Google Scholar 

  140. Nestico PF, Morganroth J, Horowitz LN. New antiarrhythmic drugs. Drugs 1988 Mar; 35(3): 286–319

    Article  PubMed  CAS  Google Scholar 

  141. Podrid PJ, Lown B. Mexiletine for ventricular arrhythmias. Am J Cardiol 1981 Apr; 47(4): 895–902

    Article  PubMed  CAS  Google Scholar 

  142. Buchert E, Woosley RL. Clinical implications of variable antiarrhythmic drug metabolism. Pharmacogenetics 1992 Feb; 2(1): 2–11

    Article  PubMed  CAS  Google Scholar 

  143. Hage K, Buhl K, Fischer C, et al. Estimation of the absolute bioavailability of flecainide using stable isotope technique. Eur J Clin Pharmacol 1995; 48(1): 51–5

    Article  PubMed  CAS  Google Scholar 

  144. Kroemer HK, Turgeon J, Parker RA, et al. Flecainide enantiomers: disposition in human subjects and electrophysiologic actions in vitro. Clin Pharmacol Ther 1989 Nov; 46(5): 584–90

    Article  PubMed  CAS  Google Scholar 

  145. Johnston A, Warrington S, Turner P. Flecainide pharmacokinetics in healthy volunteers: the influence of urinary pH. Br J Clin Pharmacol 1985 Oct; 20(4): 333–8

    Article  PubMed  CAS  Google Scholar 

  146. Galloe AM, Graudal N. Cardiac arrhythmia suppression trial. N Engl J Med 1991 Aug; 325(8): 584–5

    PubMed  CAS  Google Scholar 

  147. Somani P. Antiarrhythmic effects of flecainide. Clin Pharmacol Ther 1980 Apr; 27(4): 464–70

    Article  PubMed  CAS  Google Scholar 

  148. Bennett MI. Paranoid psychosis due to flecainide toxicity in malignant neuropathic pain. Pain 1997 Mar; 70(1): 93–4

    Article  PubMed  CAS  Google Scholar 

  149. Anderson JL, Stewart JR, Perry BA, et al. Oral flecainide acetate for the treatment of ventricular arrhythmias. N Engl J Med 1981 Aug; 305(9): 473–7

    Article  PubMed  CAS  Google Scholar 

  150. Hodges M, Haugland JM, Granrud G, et al. Suppression of ventricular ectopic depolarizations by flecainide acetate, a new antiarrhythmic agent. Circulation 1982 May; 65(5): 879–85

    Article  PubMed  CAS  Google Scholar 

  151. Meinertz T, Zehender MK, Geibel A, et al. Long-term antiarrhythmic therapy with flecainide. Am J Cardiol 1984 Jul; 54(1): 91–6

    Article  PubMed  CAS  Google Scholar 

  152. Zoble RG, Kirsten EB, Brewington J. Pharmacokinetic and pharmacodynamic evaluation of Propafenone in patients with ventricular arrhythmia. Propafenone Research Group. Clin Pharmacol Ther 1989 May; 45(5): 535–41

    Article  PubMed  CAS  Google Scholar 

  153. Funck-Brentano C, Kroemer HK, Pavlou H, et al. Genetically-determined interaction between Propafenone and low dose quinidine: role of active metabolites in modulating net drug effect. Br J Clin Pharmacol 1989 Apr; 27(4): 435–44

    Article  PubMed  CAS  Google Scholar 

  154. Siddoway LA, Thompson KA, McAllister CB, et al. Polymorphism of Propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation 1987 Apr; 75(4): 785–91

    Article  PubMed  CAS  Google Scholar 

  155. Heger JJ, Hubbard J, Zipes DP, et al. Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy. Am J Cardiol 1984 Nov; 54(9): 40D–4D

    Article  PubMed  CAS  Google Scholar 

  156. Naccarella F, Palmieri M, del Corso P, et al. Comparison of the efficacy of Propafenone versus disopyramide for complex premature ventricular contractions: evaluation with long-term monitoring. Arzneimittel Forschung 1982; 32(5): 547–50

    PubMed  CAS  Google Scholar 

  157. Prystowsky EN, Heger JJ, Chilson DA, et al. Antiarrhythmic and electrophysiologic effects of oral Propafenone. Am J Cardiol 1984 Nov; 54(9): 26D–8D

    Article  PubMed  CAS  Google Scholar 

  158. Podrid PJ, Cytryn R, Lown B. Propafenone: noninvasive evaluation of efficacy. Am J Cardiol 1984 Nov; 54(9): 53D–9D

    Article  PubMed  CAS  Google Scholar 

  159. Podrid PJ, Lown B. Propafenone: a new agent for ventricular arrhythmia. J Am Coll Cardiol 1984 Jul; 4(1): 117–25

    Article  PubMed  CAS  Google Scholar 

  160. Mason WD, Lanman RC, Kirsten EB. Plasma and saliva Propafenone concentrations at steady state. J Pharm Sci 1987 Jun; 76(6): 437–40

    Article  PubMed  CAS  Google Scholar 

  161. Salerno DM, Granrud G, Sharkey P, et al. A controlled trial of Propafenone for treatment of frequent and repetitive ventricular premature complexes. Am J Cardiol 1984 Jan; 53(1): 77–83

    Article  PubMed  CAS  Google Scholar 

  162. Kates RE, Yee YG, Winkle RA. Metabolite cumulation during chronic Propafenone dosing in arrhythmia. Clin Pharmacol Ther 1985 Jun; 37(6): 610–4

    Article  PubMed  CAS  Google Scholar 

  163. Chaudhry GM, Haffajee CI. Antiarrhythmic agents and proarrhythmia. Crit Care Med 2000; 28 Suppl. 10: N158–64

    Article  PubMed  CAS  Google Scholar 

  164. Amery A, De Plaen IF, Linjnew P. Relationship between blood level of atenolol and pharmacologic effect. Clin Pharmacol Ther 1977; 21: 691–9

    PubMed  CAS  Google Scholar 

  165. Marcus FI, Fontaine GH, Frank R, et al. Clinical pharmacology and therapeutic applications of the antiarrhythmic agent amiodarone. Am Heart J 1981 Apr; 101(4): 480–93

    Article  PubMed  CAS  Google Scholar 

  166. Singh BN, Venkatesh N, Nademanee K, et al. The historical development, cellular electrophysiology and pharmacology of amiodarone. Prog Cardiovasc Dis 1989 Jan; 31(4): 249–80

    Article  PubMed  CAS  Google Scholar 

  167. Kowey PR, Marinchak RA, Rials SJ, et al. Intravenous amiodarone. J Am Coll Cardiol 1997 May; 29(6): 1190–8

    Article  PubMed  CAS  Google Scholar 

  168. Nattel S. Comparative mechanisms of action of antiarrhythmic drugs. Am J Cardiol 1993 Nov; 72(16): 13F–7F

    Article  PubMed  CAS  Google Scholar 

  169. Pourbaix S, Berger Y, Desager JP, et al. Absolute bioavailability of amiodarone in normal subjects. Clin Pharmacol Ther 1985 Feb; 37(2): 118–23

    Article  PubMed  CAS  Google Scholar 

  170. Russo AM, Beauregard LM, Waxman HL. Oral amiodarone loading for the rapid treatment of frequent, refractory, sustained ventricular arrhythmias associated with coronary artery disease. Am J Cardiol 1993 Dec; 72(18): 1395–9

    Article  PubMed  CAS  Google Scholar 

  171. Kim SG, Mannino MM, Chou R, et al. Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading. Ann Intern Med 1992 Aug; 117(3): 197–201

    PubMed  CAS  Google Scholar 

  172. Chow MS. Intravenous amiodarone: pharmacology, pharmacokinetics, and clinical use. Ann Pharmacother 1996 Jun; 30(6): 637–43

    PubMed  CAS  Google Scholar 

  173. Flanagan RJ, Storey GC, Holt DW, et al. Identification and measurement of desethylamiodarone in blood plasma specimens from amiodarone-treated patients. J Pharm Pharmacol 1982 Oct; 34(10): 638–43

    Article  PubMed  CAS  Google Scholar 

  174. Heger JJ, Prystowsky EN, Zipes DP. Relationships between amiodarone dosage, drug concentrations, and adverse side effects. Am Heart J 1983 Oct; 106 (4 Pt 2): 931–5

    Article  PubMed  CAS  Google Scholar 

  175. Nattel S, Davies M, Quantz M. The antiarrhythmic efficacy of amiodarone and desethylamiodarone, alone and in combination, in dogs with acute myocardial infarction. Circulation 1988 Jan; 77(1): 200–8

    Article  PubMed  CAS  Google Scholar 

  176. Yabek SM, Kato R, Singh BN. Acute effects of amiodarone on the electrophysiologic properties of isolated neonatal and adult cardiac fibers. J Am Coll Cardiol 1985 May; 5(5): 1109–15

    Article  PubMed  CAS  Google Scholar 

  177. Anastasiou-Nana M, Levis GM, Moulopoulos S. Pharmacokinetics of amiodarone after intravenous and oral administration. Int J Clin Pharmacol Ther Toxicol 1982 Nov; 20(11): 524–9

    PubMed  CAS  Google Scholar 

  178. Staubli M, Bircher J, Galeazzi RL, et al. Serum concentrations of amiodarone during long term therapy: relation to dose, efficacy and toxicity. Eur J Clin Pharmacol 1983; 24(4): 485–94

    Article  PubMed  CAS  Google Scholar 

  179. Wilkinson PR, Rees JR, Storey GC, et al. Amiodarone: prolonged elimination following cessation of chronic therapy. Am Heart J 1984 Apr; 107(4): 787–8

    Article  PubMed  CAS  Google Scholar 

  180. Plomp TA, van Rossum JM, Robles de Medina EO, et al. Pharmacokinetics and body distribution of amiodarone in man. Arzneimittel Forschung 1984; 34(4): 513–20

    PubMed  CAS  Google Scholar 

  181. Giardina EG, Schneider M, Barr ML. Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation. J Am Coll Cardiol 1990 Oct; 16(4): 943–7

    Article  PubMed  CAS  Google Scholar 

  182. Falik R, Flores BT, Shaw L, et al. Relationship of steady-state serum concentrations of amiodarone and desethylamiodarone to therapeutic efficacy and adverse effects. Am J Med 1987 Jun; 82(6): 1102–8

    Article  PubMed  CAS  Google Scholar 

  183. Greenberg ML, Lerman BB, Shipe JR, et al. Relation between amiodarone and desethylamiodarone plasma concentrations and electrophysiologic effects, efficacy and toxicity. J Am Coll Cardiol 1987 May; 9(5): 1148–55

    Article  PubMed  CAS  Google Scholar 

  184. Haffajee CI, Love JC, Alpert JS, et al. Efficacy and safety of long-term amiodarone in treatment of cardiac arrhythmias: dosage experience. Am Heart J 1983 Oct; 106 (4 Pt 2): 935–43

    Article  PubMed  CAS  Google Scholar 

  185. Rotmensch HH, Belhassen B, Swanson BN, et al. Steady-state serum amiodarone concentrations: relationships with antiarrhythmic efficacy and toxicity. Ann Intern Med 1984 Oct; 101(4): 462–9

    PubMed  CAS  Google Scholar 

  186. Lee KL, Tai YT. Long-term low-dose amiodarone therapy in the management of ventricular and supraventricular tachyar-rhythmias: efficacy and safety. Clin Cardiol 1997 Apr; 20(4): 372–7

    Article  PubMed  CAS  Google Scholar 

  187. Torres V, Tepper D, Flowers D, et al. QT prolongation and the antiarrhythmic efficacy of amiodarone. J Am Coll Cardiol 1986 Jan; 7(1): 142–7

    Article  PubMed  CAS  Google Scholar 

  188. Maling TJ, Siebers RW, Burgess CD, et al. Individual variability of amiodarone distribution in plasma and erythrocytes: implications for therapeutic monitoring. Ther Drug Monit 1989; 11(2): 121–6

    Article  PubMed  CAS  Google Scholar 

  189. Ulrik CS, Backer V, Aldershvile J, et al. Serial pulmonary function tests in patients treated with low-dose amiodarone. Am Heart J 1992 Jun; 123(6): 1550–4

    Article  PubMed  CAS  Google Scholar 

  190. Gleadhill IC, Wise RA, Schonfeld SA, et al. Serial lung function testing in patients treated with amiodarone: a prospective study. Am J Med 1989 Jan; 86(1): 4–10

    Article  PubMed  CAS  Google Scholar 

  191. Singh BN, Deedwania P, Nademanee K, et al. Sotalol: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. Drugs 1987 Sep; 34(3): 311–49

    Article  PubMed  CAS  Google Scholar 

  192. Carr RA, Pasutto FM, Lewanczuk RZ, et al. Protein binding of Sotalol enantiomers in young and elderly human and rat serum using ultrafiltration. Biopharm Drug Dispos 1995 Nov; 16(8): 705–12

    Article  PubMed  CAS  Google Scholar 

  193. Brown HC, Carruthers SG, Kelly JG, et al. Observations on the efficacy and pharmacokinetics of sotalol after oral administration. Eur J Clin Pharmacol 1976 Mar; 9(5-6): 367–72

    Article  CAS  Google Scholar 

  194. Waldo AL, Camm AJ, deRuyter H, et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators: Survival With Oral d-Sotalol. Lancet 1996 Jul; 348(9019): 7–12

    Article  PubMed  CAS  Google Scholar 

  195. Waldo AL, Camm AJ, deRuyter H, et al. Survival with oral d-sotalol in patients with left ventricular dysfunction after myocardial infarction: rationale, design, and methods (the SWORD trial). Am J Cardiol 1995 May; 75(15): 1023–7

    Article  PubMed  CAS  Google Scholar 

  196. Schwartz J, Crocker K, Wynn J, et al. The antiarrhythmic effects of d-sotalol. Am Heart J 1987 Sep; 114(3): 539–44

    Article  PubMed  CAS  Google Scholar 

  197. Wang T, Bergstrand RH, Thompson KA, et al. Concentration-dependent pharmacologic properties of sotalol. Am J Cardiol 1986 May; 57(13): 1160–5

    Article  PubMed  CAS  Google Scholar 

  198. Antonaccio MJ, Gomoll A. Pharmacology, pharmacodynamics and pharmacokinetics of sotalol. Am J Cardiol 1990 Jan; 65(2): 12A–21A

    Article  PubMed  CAS  Google Scholar 

  199. Blair AD, Burgess ED, Maxwell BM, et al. Sotalol kinetics in renal insufficiency. Clin Pharmacol Ther 1981 Apr; 29(4): 457–63

    Article  PubMed  CAS  Google Scholar 

  200. Berglund G, Descamps R, Thomis JA. Pharmacokinetics of Sotalol after chronic administration to patients with renal insufficiency. Eur J Clin Pharmacol 1980 Oct; 18(4): 321–6

    Article  PubMed  CAS  Google Scholar 

  201. Kimura M, Umemura K, Ikeda Y, et al. Pharmacokinetics and pharmacodynamics of (±)-sotalol in healthy male volunteers. Br J Clin Pharmacol 1996 Nov; 42(5): 583–8

    PubMed  CAS  Google Scholar 

  202. Harron DW, Balnave K, Kinney CD, et al. Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol. Clin Pharmacol Ther 1981 Mar; 29(3): 295–302

    Article  PubMed  CAS  Google Scholar 

  203. Echizen H, Manz M, Eichelbaum M. Electrophysiologic effects of dextro- and levo-verapamil on sinus node and AV node function in humans. J Cardiovasc Pharmacol 1988; 12(5): 543–6

    Article  PubMed  CAS  Google Scholar 

  204. Echizen H, Vogelgesang B, Eichelbaum M. Effects of d,l-verapamil on atrioventricular conduction in relation to its stereoselective first-pass metabolism. Clin Pharmacol Ther 1985 Jul; 38(1): 71–6

    Article  PubMed  CAS  Google Scholar 

  205. Gross AS, Heuer B, Eichelbaum M. Stereoselective protein binding of Verapamil enantiomers. Biochem Pharmacol 1988 Dec; 37(24): 4623–7

    Article  PubMed  CAS  Google Scholar 

  206. Dominic JA, Bourne DW, Tan TG, et al. The pharmacology of Verapamil: III. pharmacokinetics in normal subjects after intravenous drug administration. J Cardiovasc Pharmacol 1981 Jan; 3(1): 25–38

    Article  PubMed  CAS  Google Scholar 

  207. Dimarco JP, Sellers TD, Berne RM, et al. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983 Dec; 68(6): 1254–63

    Article  PubMed  CAS  Google Scholar 

  208. Dimarco JP, Sellers TD, Lerman BB, et al. Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. J Am Coll Cardiol 1985 Aug; 6(2): 417–25

    Article  PubMed  CAS  Google Scholar 

  209. Berne RM, Dimarco JP, Belardinelli L. Dromotropic effects of adenosine and adenosine antagonists in the treatment of cardiac arrhythmias involving the atrioventricular node. Circulation 1984 Jun; 69(6): 1195–7

    Article  PubMed  CAS  Google Scholar 

  210. Ontyd J, Schrader J. Measurement of adenosine, inosine, and hypoxanthine in human plasma. J Chromatogr 1984 May; 307(2): 404–9

    PubMed  CAS  Google Scholar 

  211. Sollevi A. Cardiovascular effects of adenosine in man; possible clinical implications. Prog Neurobiol 1986; 27(4): 319–49

    Article  PubMed  CAS  Google Scholar 

  212. Beihassen B, Pelleg A. Adenosine triphosphate and adenosine: perspectives in the acute management of paroxysmal supraventricular tachycardia. Clin Cardiol 1985 Sep; 8(9): 460–4

    Article  Google Scholar 

  213. Klabunde RE. Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983 Sep; 93(1–2): 21–6

    Article  PubMed  CAS  Google Scholar 

  214. Ewy GA, Groves BM, Ball MF, et al. Digoxin metabolism in obesity. Circulation 1971 Nov; 44(5): 810–4

    Article  PubMed  CAS  Google Scholar 

  215. Iisalo E. Clinical pharmacokinetics of digoxin. Clin Pharmacokinet 1977 Jan; 2(1): 1–16

    Article  PubMed  CAS  Google Scholar 

  216. Koup JR, Greenblatt DJ, Jusko WJ, et al. Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. J Pharmacokinet Biopharm 1975 Jun; 3(3): 181–92

    Article  PubMed  CAS  Google Scholar 

  217. Zilly W, Richter E, Rietbrock N. Pharmacokinetics and metabolism of digoxin. Clin Pharmacol Ther 1975 Mar; 17(3): 302–9

    PubMed  CAS  Google Scholar 

  218. Kampmann J, Siersbaek-Nielsen K, Kristensen M, et al. Rapid evaluation of Creatinine clearance. Acta Med Scand 1974 Dec; 196(6): 517–20

    Article  PubMed  CAS  Google Scholar 

  219. Doherty JE, Kane JJ. Clinical pharmacology and therapeutic use of digitalis glycosides. Drugs 1973; 6(3): 182–221

    Article  PubMed  CAS  Google Scholar 

  220. Jelliffe RW. An improved method of digoxin therapy. Ann Intern Med 1968 Oct; 69(4): 703–17

    PubMed  CAS  Google Scholar 

  221. Marcus FI, Peterson A, Salel A, et al. The metabolism of tritiated digoxin in renal insufficiency in dogs and man. J Pharmacol Exp Ther 1966 Jun; 152(3): 372–82

    PubMed  CAS  Google Scholar 

  222. Smith TW, Haber E. Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration. J Clin Invest 1970 Dec; 49(12): 2377–86

    Article  PubMed  CAS  Google Scholar 

  223. Beller GA, Smith TW, Abelmann WH, et al. Digitalis intoxication: a prospective clinical study with serum level correlations. N Engl J Med 1971 May; 284(18): 989–97

    Article  PubMed  CAS  Google Scholar 

  224. Evered DC, Chapman C. Plasma digoxin concentrations and digoxin toxicity in hospital patients. Br Heart J 1971 Jul; 33(4): 540–5

    Article  PubMed  CAS  Google Scholar 

  225. Belz GG, Erbel R, Schumann K, et al. Dose-response relationships and plasma concentrations of digitalis glycosides in man. Eur J Clin Pharmacol 1978 May; 13(2): 103–11

    Article  PubMed  CAS  Google Scholar 

  226. Buch J, Waldorff S. Classical concentration-response relationship between serum digoxin level and contractility indices. Dan Med Bull 1980 Dec; 27(6): 287–90

    PubMed  CAS  Google Scholar 

  227. Hoeschen RJ, Cuddy TE. Dose-response relation between therapeutic levels of serum digoxin and systolic time intervals. Am J Cardiol 1975 Apr; 35(4): 469–72

    Article  PubMed  CAS  Google Scholar 

  228. Ordog GJ, Benaron S, Bhasin V, et al. Serum digoxin levels and mortality in 5100 patients. Ann Emerg Med 1987 Jan; 16(1): 32–9

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark

    Gesche Jürgens

  2. Department of Internal Medicine and Rheumatology Q, Copenhagen University Hospital of Herlev, Herlev, Denmark

    Niels A. Graudal

  3. Institute of Rational Pharmacotherapy, Medicines Agency, Copenhagen, Denmark

    Jens P. Kampmann

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Jürgens, G., Graudal, N.A. & Kampmann, J.P. Therapeutic Drug Monitoring of Antiarrhythmic Drugs. Clin Pharmacokinet 42, 647–664 (2003). https://doi.org/10.2165/00003088-200342070-00004

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