Medical Toxicology and Adverse Drug Experience

, Volume 4, Issue 6, pp 412–428 | Cite as

Poisoning Due to Class 1B Antiarrhythmic Drugs

Lignocaine, Mexiletine and Tocainide
  • Charles P. Denaro
  • Neal L. Benowitz
Toxicology Management Review


Since most of the toxicity associated with class 1B antiarrhythmic drugs is dose-related, this review examines adverse effects seen in both therapeutic practice and accidental or premeditated overdose. Toxicity is very common with these agents and can be life-threatening. A high percentage of patients must discontinue therapy because of adverse effects. Mexiletine and tocainide are structural analogues of lignocaine (lidocaine) and toxicity is similar with all 3 drugs.

With gradual intoxication (the most common form) central nervous system effects such as lightheadedness, dizziness, drowsiness and confusion are seen first. Seizures and respiratory arrest can occur. Cardiovascular toxicity is manifested by progressive heart block, reduced cardiac contraction, hypotension and asystole. Both mexiletine and tocainide may have proarrhythmic effects. Gastrointestinal toxicity is also common.

Shock, hypotension, cardiac failure and β-blocker therapy reduce lignocaine clearance and enhance the risk of intoxication during routine therapy. Both lignocaine and mexiletine elimination is impaired in severe liver disease while tocainide clearance is reduced in renal failure.

Management of toxicity is largely supportive and symptomatic. Lignocaine infusion must be discontinued and decontamination of the gut in the case of oral preparations is recommended. Serious intoxication requires intensive care unit admission. Haemodialysis or haemoperfusion may be helpful in serious lignocaine and tocainide poisoning. In institutions where extracorporeal circulatory assistance is available, massive lignocaine poisoning has been successfully treated with this intervention.

In the therapeutic setting serious toxicity can be prevented by close clinical surveillance and appropriate dose reduction in patients with reduced drug clearance. Because of the large interindividual variation in lignocaine pharmacokinetic parameters, therapeutic drug monitoring is recommended if results can be reported quickly. Mexiletine and tocainide have stereoselective metabolism and assays do not distinguish the more active isomers. Therapeutic drug monitoring is less useful in this situation.


Lidocaine Therapeutic Drug Monitoring Lignocaine Mexiletine American Heart Journal 
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  1. Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. Journal of Cardiovascular Pharmacology 5: 1093–1096, 1983PubMedCrossRefGoogle Scholar
  2. Adriani J, Zepernick R, Hyde E. Influence of the status of the patient on systemic effects of local anesthetic agents. Anesthetics and Analgesia 45: 87–92, 1966Google Scholar
  3. Alfano SN, Leicht MJ, Skiendzielewski JJ. Lidocaine toxicity following subcutaneous administration. Annals of Emergency Medicine 13: 465–467, 1984PubMedCrossRefGoogle Scholar
  4. Arrowsmith JB, Creamer JI, Bosco L. Severe dermatologic reactions reported after treatment with tocainide. Annals of Internal Medicine 107: 693–696, 1987PubMedGoogle Scholar
  5. Badui E, Garcia-Rubi D, Estanol B. Inadvertent massive lidocaine overdose causing temporary complete heart block in myocardial infarction. American Heart Journal 102: 801–803, 1981PubMedCrossRefGoogle Scholar
  6. Barchowsky A, Shand DG, Stargel WW, Wagner GS, Routledge PA. On the role of alpha 1-acid glycoprotein in lignocaine accumulation following myocardial infarction. British Journal of Clinical Pharmacology 13: 411–415, 1982PubMedCrossRefGoogle Scholar
  7. Barnfield J, Kemmenoe AV. A sudden death due to tocainide overdose. Human Toxicology 5: 337–340, 1986PubMedCrossRefGoogle Scholar
  8. Bauer LA, Brown T, Gibaldi M, Hudson L, Nelson S, et al. Influence of long-term infusions on lidocaine kinetics. Clinical Pharmacology and Therapeutics 31: 433–437, 1982PubMedCrossRefGoogle Scholar
  9. Benowitz N, Forsyth RP, Melmon KL, Rowland M. Lidocaine disposition kinetics in monkey and man. 1. Prediction by a perfusion model. Clinical Pharmacology and Therapeutics 16: 87–98, 1974PubMedGoogle Scholar
  10. Benowitz NL, Meister W. Pharmacokinetics in patients with cardiac failure. Clinical Pharmacokinetics 1: 389–405, 1976PubMedCrossRefGoogle Scholar
  11. Benowitz NL, Meister W. Clinical pharmacokinetics of lignocaine. Clinical Pharmacokinetics 3: 177–201, 1978PubMedCrossRefGoogle Scholar
  12. Bigger T. The interaction of mexiletine with other cardiovascular drugs. American Heart Journal 107: 1079–1085, 1984PubMedCrossRefGoogle Scholar
  13. Binnion PF, Murtagh G, Pollock AM, Fletcher E. Relation between plasma lignocaine levels and induced hemodynamic changes. British Medical Journal 3: 390–392, 1969PubMedCrossRefGoogle Scholar
  14. Blumer J, Strong JM, Atkinson AJ. The convulsant potency of lidocaine and its N-dealkylated metabolites. Journal of Pharmacology and Experimental Therapeutics 186: 31–36, 1973PubMedGoogle Scholar
  15. Boston Collaborative Drug Surveillance Program. Drug-induced convulsions. Lancet 2: 677, 1972Google Scholar
  16. Campbell RWF. Mexiletine. New England Journal of Medicine 316: 29–34, 1987PubMedCrossRefGoogle Scholar
  17. Cheng TO, Wadhwa K. Sinus standstill following intravenous lidocaine administration. Journal of the American Medical Association 223: 790–792, 1973PubMedCrossRefGoogle Scholar
  18. Chow MSS, Ronfeldt RA, Ruffet D, Fieldman A. Lidocaine pharmacokinetics during cardiac arrest and external cardiopulmonary resuscitation. American Heart Journal 102: 799–801, 1981PubMedCrossRefGoogle Scholar
  19. Chow MSS, Ronfeldt RA, Hamilton RA, Helmink R, Fieldman A. Effect of external cardiopulmonary resuscitation on lidocaine pharmacokinetics in dogs. Journal of Pharmacology and Experimental Therapeutics 224: 531–537, 1983PubMedGoogle Scholar
  20. Clarke CWF, El-Mahdi EO. Fatal oral tocainide overdosage. British Medical Journal 288: 760, 1984CrossRefGoogle Scholar
  21. Cocco G, Strozzi C, Chu D, Pansini R. Torsades de pointes as a manifestation of mexiletine toxicity. American Heart Journal 100: 878–880, 1980PubMedCrossRefGoogle Scholar
  22. Cohen A. Accidental overdose of tocainide successfully treated. Angiology 38: 614, 1987PubMedCrossRefGoogle Scholar
  23. Collinsworth KA, Strong JM, Atkinson Jr AJ, Winkie RA, Perlroth F, et al. Pharmacokinetics and metabolism of lidocaine in patients with renal failure. Clinical Pharmacology and Ther-apeutics 18: 59–64, 1975Google Scholar
  24. Covino BG. Pharmacology of local anesthetic agents. Rational Drug Therapy 21: 1–9, 1987PubMedGoogle Scholar
  25. Davison R, Parker M, Atkinson AJ. Excessive serum lidocaine levels during maintenance infusions: Mechanisms and prevention. American Heart Journal 104: 203–207, 1982PubMedCrossRefGoogle Scholar
  26. Davis LD, Temte JV. Electrophysiological action of lidocaine on canine ventricular muscle and Purkinje fibres. Circulation Research 24: 639–655, 1969PubMedCrossRefGoogle Scholar
  27. Drayer DE, Lorenzo B, Werns S, Reidenberg MM. Plasma levels, protein binding and elimination data of lidocaine and active metabolites in cardiac patients of various ages. Clinical Pharmacology and Therapeutics 34: 14–22, 1983PubMedCrossRefGoogle Scholar
  28. Edgren B, Tilelli J, Gehrz R. Intravenous lidocaine overdosage in a child. Clinical Toxicology 24: 51–58, 1986PubMedCrossRefGoogle Scholar
  29. Elder JL, Smith WG. Dangers of lignocaine. British Journal of Medicine 1: 1416–1417, 1964CrossRefGoogle Scholar
  30. Engler RL, Le Winter M. Tocainide-induced ventricular fibrillation. American Heart Journal 101: 494–496, 1981PubMedCrossRefGoogle Scholar
  31. Englesson S, Paymaster NJ, Hill TR. Electrical seizure activity produced by xylocaine and citanest. Acta Anacsthesiologica Scandinavica 16: 47–50, 1965CrossRefGoogle Scholar
  32. Fasola GP, D’Osualdo F, de Panghcr V, Barducci E. Thrombocytopenia and mexiletine. Annals of Internal Medicine 100: 162, 1984PubMedGoogle Scholar
  33. Fenster PE, Kern KB. Mexiletine in refractory ventricular arrhythmias. Clinical Pharmacology and Therapeutics 34: 777–784, 1983PubMedCrossRefGoogle Scholar
  34. Finkelstein F, Kreeft J. Massive lidocaine poisoning. New England Journal of Medicine 301: 50, 1979PubMedCrossRefGoogle Scholar
  35. Follath F, Ganzinger U, Schuetz E. Reliability of antiarrhythmic drug plasma concentration monitoring. Clinical Pharmacokinetics 8: 63–82, 1983PubMedCrossRefGoogle Scholar
  36. Freedman MD, Gal J, Freed CR. Extracorporeal pump assistance —novel treatment for acute lidocaine poisoning. European Journal of Clinical Pharmacology 22: 129–135, 1982PubMedCrossRefGoogle Scholar
  37. Fruncillo RJ, Gibbons W, Bowman SM. CNS toxicity after ingestion of topical lidocaine. New England Journal of Medicine 306: 426–427, 1982PubMedGoogle Scholar
  38. Gamble OW, Cohn K. Effect of propranolol, procainamide and lidocaine in ventricular automaticity and reentry in experimental myocardial infarction. Circulation 46: 498–506, 1972PubMedCrossRefGoogle Scholar
  39. Geddes JS, Webb S, Pantridge JF. Limitation of lignocaine in control of early ventricular dysrhythmias complicating acute myocardial infarction. British Heart Journal 7: 964–965, 1972Google Scholar
  40. Gerstenblith G, Spear JF, Moore EN. Quantitative study of the effect of lidocaine on the threshold for ventricular fibrillation in the dog. American Journal of Cardiology 30: 242–247, 1972PubMedCrossRefGoogle Scholar
  41. Graham CF, Turner WM, Jones JK. Lidocaine-propranolol interactions. New England Journal of Medicine 304: 1301, 1980Google Scholar
  42. Graffner C, Conradson TB, Hofvendahl S, Ryden L. Tocainide kinetics after intravenous and oral administration in healthy subjects and in patients with acute myocardial infarction. Clinical Pharmacology and Therapeutics 27: 64–71, 1980PubMedCrossRefGoogle Scholar
  43. Grech Belanger O, Turgeon J, Gilbert M. Stereoselective disposition of mexiletine in man. British Journal of Clinical Pharmacology 21: 481–487, 1986PubMedCrossRefGoogle Scholar
  44. Greenblatt DJ, Benjamin DM, Willis CR, Harmatz JS, Zinny MA. Lidocaine plasma concentrations following administration of intraoral lidocaine solution. Archives of Otolaryngology 111: 298–300, 1985PubMedCrossRefGoogle Scholar
  45. Grimes DA, Cates W. Deaths from paracervical anesthesia used for first trimester abortion. New England Journal of Medicine 295: 1397–1399, 1976PubMedCrossRefGoogle Scholar
  46. Gupta PK, Lichstein E, Chadda KD. Lidocaine-induced heart block in patients with bundle branch block. American Journal of Cardiology 33: 487–492, 1974PubMedCrossRefGoogle Scholar
  47. Halkin H, Meffin P, Melmon KL, Rowland M. Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite. Clinical Pharmacology and Therapeutics 17: 669–676, 1975PubMedGoogle Scholar
  48. Hess GP, Walson PD. Seizures secondary to oral viscous lidocaine. Annals of Emergency Medicine 17: 725–727, 1988PubMedCrossRefGoogle Scholar
  49. Holmes GI, Shapiro DA, Nicolodi LK, Irvin JD. Letter to the editor. New England Journal of Medicine 316: 344, 1987Google Scholar
  50. Horn HR, Hadidian Z, Johnson JL, Vassallo HG, Williams JH, et al. Safety evaluation of tocainide in the American Emergency Use Program. American Heart Journal 100: 1037–1040, 1980PubMedCrossRefGoogle Scholar
  51. Howard JJ, Mohsenifar Z, Simons SM. Adult respiratory distress syndrome following administration of lidocaine. Chest 81: 644–645, 1982PubMedCrossRefGoogle Scholar
  52. Ikram H. Hemodynamic and electrophysiological interactions between antiarrhythmic drugs and beta blockers, with special reference to tocainide. American Heart Journal 100: 1076–1080, 1980PubMedCrossRefGoogle Scholar
  53. Jackson JE, Bentley JB, Glass SJ, Fukui T, Gandolfi AJ, et al. Effects of hislaminc-2 receptor blockade on lidocaine kinetics. Clinical Pharmacology and Therapeutics 37: 544–548, 1985PubMedCrossRefGoogle Scholar
  54. Jequier P, Jones R, Mackintosh A. Fatal mcxiletine overdose. Lancet 1: 429, 1976PubMedCrossRefGoogle Scholar
  55. Jewitt DE, Kishon Y, Thomas M. Lignocaine in the management of arrhythmias after acute myocardial infarction. Lancet 1: 266–270, 1968CrossRefGoogle Scholar
  56. Kao FF, Jalar UH. The central action of lignocaine and its effect on cardiac output. British Journal of Pharmacology 14: 522–526, 1959Google Scholar
  57. Kempen PM. Lethal/toxic injection of 20% lidocainc: a well-known complication of an unnecessary preparation? Anesthesiology 65: 564–565, 1986PubMedCrossRefGoogle Scholar
  58. Kim WY, Pomcrance JJ, Miller AA. Lidocaine intoxication in a newborn following local anesthesia for episiotomy. Pediatrics 64: 643–645, 1979PubMedGoogle Scholar
  59. Klein MD, Levine PA, Ryan TJ. Antiarrhythmic efficacy, pharmacokinetics and clinical safety of tocainide in convalescent myocardial infarction patients. Chest 77: 726–730, 1980PubMedCrossRefGoogle Scholar
  60. Kupersmith J, Antman EM, Hoffman BF. In vivo electrophysiological effects of lidocainc in canine acute myocardial infarction. Circulation Research 36: 84–91, 1976CrossRefGoogle Scholar
  61. Lennard MS, Tucker GT, Woods HF. Time-dependent kinetics of lignocaine in the isolated perfused rat liver. Journal of Pharmacokinetics and Biopharmaceutics 11: 165–182, 1983PubMedGoogle Scholar
  62. LeLorier J, Grenon D, Latour Y, Caille G, Dumont G, et al. Pharmacokinetics of lidocaine after prolonged intravenous infusions in uncomplicated myocardial infarction. Annals of Internal Medicine 87: 700–702, 1977aPubMedGoogle Scholar
  63. LeLorier J, Moisan R, Gagne J, Caille G. Effect of the duration of infusion on the disposition of lidocaine in dogs. Journal of Pharmacology and Experimental Therapeutics 203: 507–511, 1977bPubMedGoogle Scholar
  64. Lichstein E, Chadda KD, Gupta PK. Atrioventricular block with lidocaine therapy. American Journal of Cardiology 31: 277–281, 1973PubMedCrossRefGoogle Scholar
  65. Lie KI, Welleng HJ, van Capelle FJ, Durrer D. Lidocaine in the prevention of primary ventricular fibrillation. New England Journal of Medicine 291: 1324–1326, 1974PubMedCrossRefGoogle Scholar
  66. Luchi RJ, Helwig J, Conn HL. Quinidine toxicity and its treatment. An experimental study. American Heart Journal 65: 340–348, 1963CrossRefGoogle Scholar
  67. Mitchell BG, Clements JA, Pottage A, Prescott LF. Mexiletine disposition. British Journal of Clinical Pharmacology 16: 281–284, 1983PubMedCrossRefGoogle Scholar
  68. Noble J, Kennedy DJ, Latimer RD, Hardy I, Bethune DW, et al. Massive lignocainc overdose during cardiopulmonary bypass: successful treatment with cardiac pacing. British Journal of Anaesthesia 56: 1439–1441, 1984PubMedCrossRefGoogle Scholar
  69. O’Donohue WJ, Moss LM, Angelillo VA. Acute methemoglobinemia induced by topical benzocaine and lidocaine. Archives of Internal Medicine 140: 1508–1509, 1980PubMedCrossRefGoogle Scholar
  70. Peat MA, Deyman ME, Crouch DJ, Margot P, Finkle BS. Concentrations of lidocainc and monoethylglycylxylididc (MEGX) in lidocaine associated deaths. Journal of Forensic Sciences 30: 1048–1057, 1985PubMedGoogle Scholar
  71. Pernot C, Marcon F, Weber JL, Netter P, Trechot P. Effets indesirables hepatiques de la mexiletine: à propos de 6 observation. Therapie 38: 695–700, 1983Google Scholar
  72. Pentikainen PJ, Halinen MO, Helin MJ. Pharmacokinctics of oral mexiletine in patients with acute myocardial infarction. European Journal of Clinical Pharmacology 25: 773–777, 1983PubMedCrossRefGoogle Scholar
  73. Pfeifer HJ, Greenblatt DJ, Koch-Weser J. Clinical use and toxicity of intravenous lidocaine: a report from the Boston Collaborative Drug Surveillance Program. American Heart Journal 92: 168–173, 1976PubMedCrossRefGoogle Scholar
  74. Podrid PJ, Lown B. Mexiletine for ventricular arrhythmias. American Journal of Cardiology 47: 895–902, 1981PubMedCrossRefGoogle Scholar
  75. Poklis A, Mackell MA, Tucker EF. Tissue distribution of lidocaine after fatal accidental injection. Journal of Forensic Sciences 29: 1229–1236, 1984PubMedGoogle Scholar
  76. Prescott F, Adjepon-Yamoah KK, Talbot RG. Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure. British Medical Journal 1: 939–941, 1976PubMedCrossRefGoogle Scholar
  77. Rademaker AW, Kellen J, Tarn YK, Wyse DG. Character of adverse effects of prophylactic lidocaine in the coronary care unit. Clinical Pharmacology and Therapeutics 40: 71–80, 1986PubMedCrossRefGoogle Scholar
  78. Ritchie JM, Green NM. Local anesthetics. In Goodman et al. (Eds) Pharmacological Basis of Therapeutics, 7th ed., pp. 302–321, Macmillan, New York, 1985Google Scholar
  79. Rizzon P, Di Biase M, Favale S, Visani L. Class 1B agents lidocaine, mexiletine, tocainide, phenytoin. European Heart Journal 8 (Suppl. A): 21–25, 1987PubMedCrossRefGoogle Scholar
  80. Roden DM, Woosley RL. Tocainide. New England Journal of Medicine 315: 41–45, 1986PubMedCrossRefGoogle Scholar
  81. Roos JC, Paalman ACA, Dunning AJ. Electrophysiological effects of mexiletine in man. British Heart Journal 38: 1262–1271, 1976PubMedCrossRefGoogle Scholar
  82. Routledge PA, Stargel WW, Wagner GS, Shand DG. Increased alpha-1-acid glycoprotein and lidocaine disposition in myocardial infarction. Annals of Internal Medicine 93: 701–704, 1980PubMedGoogle Scholar
  83. Ryan W, Engler R, LeWinter M, Karliner JS. Efficacy of a new oral agent (tocainide) in the acute treatment of refractory ventricular arrhythmias. American Journal of Cardiology 43: 285–300, 1979PubMedCrossRefGoogle Scholar
  84. Saravay SM, Marke J, Steinberg MD, Rabiner CJ. Doom anxiety and delirium in lidocaine toxicity. American Journal of Psychiatry 144: 159–163, 1987PubMedGoogle Scholar
  85. Sawyer DR, Ludden TM, Crawford MH. Continuous infusion of lignocaine in patients with cardiac arrhythmias: unpredictability of plasma concentrations. Archives of Internal Medicine 141: 43–45, 1981PubMedCrossRefGoogle Scholar
  86. Schrader BJ, Bauman JL. Mexiletine: a new type I antiarrhythmic agent. Drug Intelligence and Clinical Pharmacy 20: 255–260, 1986PubMedGoogle Scholar
  87. Schuster MR, Paris PM, Kaplan RM, Stewart RD. Effect on the seizure threshold in dogs of tocainide/lidocaine administration. Annals of Emergency Medicine 16: 749–751, 1987PubMedCrossRefGoogle Scholar
  88. Sedman AJ, Gal J, Mastropaolo W, Johnson P, Maloney JD, et al. Serum tocainide enantiomer concentrations in human subjects. British Journal of Clinical Pharmacology 17: 113–115, 1984PubMedCrossRefGoogle Scholar
  89. Sperry K, Wohlenberg N, Standefer KC. Fatal intoxication by tocainide. Journal of Forensic Sciences 32: 1440–1446, 1987PubMedGoogle Scholar
  90. Strichartz GR. Current concepts of the mechanism of action of local anesthetics. Journal of Dental Research 60: 1460–1467, 1981PubMedCrossRefGoogle Scholar
  91. Strong JM, Parker M, Atkinson AJ. Identification of glycinexylidide in patients treated with intravenous lidocaine. Clinical Pharmacology and Therapeutics 14: 67–72, 1973PubMedGoogle Scholar
  92. Strong JM, Mayfield DE, Atkinson AJ, Burris BC, Raymon F, et al. Pharmacological activity, metabolism, and pharmacokinetics of glycinexylidide. Clinical Pharmacology and Therapeutics 17: 184–194, 1975PubMedGoogle Scholar
  93. Svendsen TL, Tango M, Waldorff S, Steiness E, Trap-Jensen J. Effects of propranolol and pindolol on plasma lignocaine clearance in man. British Journal of Clinical Pharmacology 13: 223S–226S, 1982PubMedCrossRefGoogle Scholar
  94. Thomson AH, Kelman AW, de Vane PJ, Stewart Hillis W, Whiting B. Changes in lignocaine disposition during long-term infusion in patients with acute ventricular arrhythmias. Therapeutic Drug Monitoring 9: 283–291, 1987aPubMedCrossRefGoogle Scholar
  95. Thomson AH, Elliott HL, Kelman AW, Meredith PA, Whiting B. The pharmacokinetics and pharmacodynamics of lignocaine and MEGX in healthy subjects. Journal of Pharmacokinetics and Biopharmaceutics 15: 101–115, 1987bPubMedGoogle Scholar
  96. Thomson PD, Rowland M, Melmon KL. The influence of heart failure, liver disease, and renal failure on the disposition of lidocaine in man. American Heart Journal 82: 417–421, 1971PubMedCrossRefGoogle Scholar
  97. Vozeh S, Katz G, Steiner V, Follath F. Population pharmacokinetic parameters in patients treated with oral mexiletine. European Journal of Clinical Pharmacology 23: 445–451, 1982PubMedCrossRefGoogle Scholar
  98. Vozeh S, Berger M, Wenk M, Ritz R, Follath F. Rapid prediction of individual dosage requirements for lignocaine. Clinical Pharmacokinetics 9: 354–363, 1984PubMedCrossRefGoogle Scholar
  99. Vozeh S, Uematsu T, Ritz R, Schmidlin O, Kaufman G, et al. Computer-assisted individualized lidocaine dosage: clinical evaluation and comparison with physician performance. American Heart Journal 113: 928–933, 1987PubMedCrossRefGoogle Scholar
  100. Wiegers U, Hanrath P, Kuck KH, Pottage A, Graffner C, et al. Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis. European Journal of Clinical Pharmacology 24: 503–507, 1983PubMedCrossRefGoogle Scholar
  101. Woods LA, Haggart J. Apneic and hypotensive effects of local anesthetic drugs in dogs and mice under general anesthesia. Anesthesiology 18: 831–840, 1957PubMedCrossRefGoogle Scholar
  102. Zito RA, Reid PR, Longstretch JA. Variability of early lignocaine levels in patients. American Heart Journal 94: 292–296, 1977PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • Charles P. Denaro
    • 1
  • Neal L. Benowitz
    • 1
  1. 1.Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, Department of MedicineUniversity of CaliforniaSan FranciscoUSA

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