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Immunotherapy for Drug Toxicity

  • Chapter
Therapeutic Antibodies

Abstract

The potential use of immunotherapy in the treatment of drug-induced toxicity has been recognized for decades (Colburn 1980). Antibodies have been raised in horses, rats, rabbits, sheep and goats against a variety of drugs such as aspirin (Hooker and Boyd 1940), chloramphenicol (Hamburger and Douglass 1969), colchicine (Terrien et al. 1990), strychnine (Hooker and Boyd 1940), digoxin (Butler and Chen 1967), imipramine (O’Callaghan et al. 1987), desmethylimipramine (Pond et al. 1991), nortriptyline (Sabouraud et al. 1990), amitriptyline (Sidki 1991, personal communication) and phencyclidine (Owens and Mayersohn 1986). However, only one product - digoxin-speeific ovine Fab fragments (Digibind, Digidote) - is marketed. This treatment has been available for almost 20 years yet remains the only commercially available immunotherapeutic antidote against drug-induced poisoning. Why is this so?

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References

  • Aeberhard P, Butler V-P, Smith TW et al (1980) Le traitement d’une intoxication digitalique massive (20 mg de digitoxine) par les anticorps anti-digoxine fractionnĂ©s (Fab). Arch Mai Coeur 12: 1471–1478

    Google Scholar 

  • Allen NM, Dunham DG, Sailstad JM, Findlay JW (1991) Clinical and pharmacokinetic profiles of digoxin-immune Fab in four patients with renal impairment. Drug Intell Clin Pharm 25:1315–1320

    CAS  Google Scholar 

  • Antman EM, Wenger TL, Butler VP, Haber E, Smith TW (1990) Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation 81: 1744–1752

    Article  PubMed  CAS  Google Scholar 

  • Baud FJ, Scherrmann JM, Sabouraud A, Taboulet P (1992) Clinical course of one life-threatening colchicine intoxication treated with colchicine-specific Fab fragments. Proceedings of the XV European Association of Poison Centres and Clinical Toxicology Congress, Istanbul, 1992

    Google Scholar 

  • Bayer M (1991) Recognition and management of digitalis intoxication. Am J Emerg Med 9 (suppl 1): 29–32

    Article  PubMed  CAS  Google Scholar 

  • Bismuth C, Baud F, Dally S (1986) Standardized prognosis evaluation in acute toxicology. Its benefit in colchicine, paraquat and digitalis poisonings. J Toxicol Clin Toxicol 6: 33–38

    CAS  Google Scholar 

  • Bismuth C, Motte G, Conso F, Chauvin M, Gaultier M (1977) Acute digitoxin intoxication treated by intracardiac pacemaker: Experience in sixty-eight patients. Clin Toxicol 10: 443–456

    Article  PubMed  CAS  Google Scholar 

  • Blum LM, Rieders F (1987) Oleandrin distribution in a fatality from rectal and oral Nerium oleander extract administration. J Anal Toxicol 11: 219–221

    PubMed  CAS  Google Scholar 

  • Bouffard Y, Bui Xuan B, Roux H et al. (1982) Intoxication Ă  la digitoxine. Traitment par des fragments Fab d’anticorps anti-digoxine. La Nouvelle Presse Medicale 11(39): 29–28

    Google Scholar 

  • Brunn GJ, Keyler DE, Pond SM, Pentel PR (1992) Reversal of desipramine toxicity in rats using drug specific antibody Fab′ fragment: Effects on hypotension and interaction with sodium bicarbonate. J Pharmacol Exp Ther 260(3): 1392–1399

    PubMed  CAS  Google Scholar 

  • Brunn GJ, Keyler DE, Ross CA, Pond SM, Pentel PR (1991) Drug specific F(ab′)2 fragment reduces desipramine cardiotoxicity in rats. Int J Immunopharmacol 13(7): 841–852

    Article  PubMed  CAS  Google Scholar 

  • Butler VP, Chen JP (1967) Digoxin specific antibodies. Proc Natl Acad Sci USA 57: 71–78

    Article  PubMed  CAS  Google Scholar 

  • Clark RF, Selden BS, Curry SC (1991) Digoxin specific Fab fragments in the treatment of oleander toxicity in a canine model. Ann Emerg Med 20(10): 1073–1077

    Article  PubMed  CAS  Google Scholar 

  • Clifton GD, Mclntyre WJ, Zannikos PN, Harrison MR, Chandler MH (1989) Free and total serum digoxin concentrations in a renal failure patient after treatment with digoxin immune Fab. Clin Pharmacol 8: 441–445

    CAS  Google Scholar 

  • Colburn WA (1980) Specific antibodies and Fab fragments to alter the pharmacokinetics and reverse pharmacologic/toxicologic effects of drugs. Drug Metab Rev 11(2): 223–262

    Article  PubMed  CAS  Google Scholar 

  • Colucci RD, Chow M, Kluger J et al (1989) The pharmacokinetics of digoxin immune Fab, total digoxin and free digoxin in patients with renal impairment. Pharmacotherapy 9: 175 (abst)

    Google Scholar 

  • Cummins RO, Haulman J, Quan L, Graves JR, Peterson D, Horan S (1990) Near-fatal yew berry intoxication treated with external cardiac pacing and digoxin-specific Fab antibody fragments. Ann Emerg Med 19: 38–43

    Article  PubMed  CAS  Google Scholar 

  • Curd J, Smith TW, Jaton J (1971) The isolation of digoxin specific antibodies and its use in reversing the effects of digoxin. Proc Natl Acad Sci USA 68: 2401–2406

    Article  PubMed  CAS  Google Scholar 

  • Ellenhora MJ, Barceloux DG (1988) Medical toxicology. Diagnosis and treatment of human poisoning. Elsevier, New York

    Google Scholar 

  • Erdmann E, Mair W, Knedel M, Schaumann W (1989) Digitalis intoxication and treatment with digoxin antibody fragments in renal failure. Klin Wochenschr 67: 16–19

    Article  PubMed  CAS  Google Scholar 

  • Frommer DA, Kulig KA, Marx JA, Rumack B (1987) Tricyclic antidepressant overdose. JAMA 257: 521–526

    Article  PubMed  CAS  Google Scholar 

  • Goodlin RC (1988) Antidigoxin antibodies in eclampsia. N Engl J Med 318(8): 518

    Article  PubMed  CAS  Google Scholar 

  • Hamburger RN, Douglass JH (1969) Chloramphenicol-specific antibody. II. Reactivity to analogues of chloramphenicol. Immunology 17(4): 587–591

    PubMed  CAS  Google Scholar 

  • Heath A, Wickström I, Ahlmen J, MĂĄrtensson E (1982) Treatment of antidepressant poisoning with resin haemoperfusion. Human Toxicol 1(4): 152–156

    Google Scholar 

  • Hickey AR, Wenger TL, Carpenter VP et al. (1991) Digoxin immune Fab therapy in the management of digitalis intoxication: Safety and efficacy. Results of an observational surveillance study. J Am Coll Cardiol 17(3): 590–598

    Article  PubMed  CAS  Google Scholar 

  • Hooker SB, Boyd WC (1940) Antibodies to strychnine. J Immunol 38: 479–490

    CAS  Google Scholar 

  • Huang CT, Smith RM (1984) Lowering of blood pressure in chronic aortic coarctate hypertensive rats with antidigoxin antiserum. Life Sci 35: 115–118

    Article  PubMed  CAS  Google Scholar 

  • HultĂ©n B-A, Heath A (1983) Clinical evaluation of tricyclic antidepressant poisoning. Acta Med Scand 213: 275–278

    Article  PubMed  Google Scholar 

  • HultĂ©n B-A, Heath A, Knudsen K, Nyberg G, Starmark J-E, MĂĄrtensson E (1992) Severe amitriptyline overdose: Relationship between toxicokinetics and toxicodynamics. J Toxicol Clin Toxicol 30(2): 171–179

    Article  PubMed  Google Scholar 

  • Hursting MJ, Opheim KE, Raisys CA, Kenny MA, Metzger G (1989) Tricyclic antidepressant-specific Fab fragments alter distribution and elimination in the rabbit: A model for overdose treatment. J Toxicol Clin Toxicol 27: 53–66

    Article  PubMed  CAS  Google Scholar 

  • Jaeger A, Berton C, Kopferschmitt J et al. (1992) Dosing with digoxin-Fab fragments. Proceedings of the XV European Association of Poison Centres and Clinical Toxicology Congress, Istanbul, 1992

    Google Scholar 

  • Keyler DE, Murakami MA, Salerno DM, Ruth GR, Pentel PR (1990) Toxicity and pharmacokinetics of high doses of antibody Fab fragments in dogs. Vet Hum Toxicol 32(4): 341 (abstr)

    Google Scholar 

  • Kirkpatrick CH (1991) Allergic histories and reactions of patients treated with digoxin immune Fab (ovine) antibody. Am J Emerg Med 9 (suppl 1): 7–10

    Article  PubMed  CAS  Google Scholar 

  • Kunes J, Stolba P, Pohlova I, Jelinek J, Zicha J (1985) The importance of digoxin-like factors in rats with various forms of experimental hypertension. Clin Exp Hypertens 7: 707–720 (abstr)

    Article  CAS  Google Scholar 

  • Lewander WJ, Gauldreault P, Einhorn H, Henretig FM, Lacouture PG, Lovejoy FH (1986) Acute pediatric digoxin ingestion: A ten year experience. Am J Dis Child 140: 770–773

    PubMed  CAS  Google Scholar 

  • Lloyd BL, Smith TW (1978) Contrasting rates of reversal of digoxin toxicity by digoxin specific IgG and Fab fragments. Circulation 58: 280–283

    PubMed  CAS  Google Scholar 

  • Mahdyoon H, Battilana G, Rosman H, Goldstein S, Gheorghiade M (1990) The evolving pattern of digoxin intoxication: Observations at a large urban hospital from 1980–1988. Am Heart J 120(5): 1189–1194

    Article  PubMed  CAS  Google Scholar 

  • Marchlinski FE, Hook BG, Callans DJ (1991) Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Am J Emerg Med 9 (suppl 1): 24–28

    Article  PubMed  CAS  Google Scholar 

  • Nuwayhid NF, Johnson GF (1989) Digoxin elimination in a functionally anephric patient after digoxin-specific Fab fragment therapy. Ther Drug Monit 11: 680–685

    Article  PubMed  CAS  Google Scholar 

  • O’Callaghan AM, Phillips OM, Williams DC (1987) Antisera raised against the drug imipramine. J Neurochem 49(4): 1091–1095

    Article  PubMed  Google Scholar 

  • Osterloh J, Herold S, Pond SM (1982) Oleander interference in the digoxin radioimmunoassay in a fatal ingestion. JAMA 247: 1596–1597

    Article  PubMed  CAS  Google Scholar 

  • Owens SM, Mayersohn M (1986) Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs. Drug Metab Dispos 14: 52–58

    PubMed  CAS  Google Scholar 

  • Pentel PR, Benowitz NL (1984) Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats. J Pharmacol Exp Ther 230: 12–19

    PubMed  CAS  Google Scholar 

  • Pentel PR, Keyler DE (1988) Effect of high dose alpha-1-acid glycoprotein on desipramine toxicity in rats. J Pharmacol Exp Ther 246: 1061–1066

    PubMed  CAS  Google Scholar 

  • Pentel P, Pond SM, Schoof D (1987) Redistribution into plasma of tracer doses of desipramine by anti-desipramine antiserum in rats. Biochem Pharmacol 36(2): 293–295

    Article  PubMed  CAS  Google Scholar 

  • Pentel PR, Keyler DE, Brunn GJ et al. (1991a) Redistribution of tricyclic antidepressants in rats using a drug-specific monoclonal antibody: Dose-response relationship. Drug Metab Dispos 19: 24–28

    PubMed  CAS  Google Scholar 

  • Pentel PR, Brunn GJ, Pond SM, Keyler DE (1991b) Pretreatment with drug specific antibody reduces desipramine cardiotoxicity in rats. Life Sci 48(7): 675–683

    Article  PubMed  CAS  Google Scholar 

  • Persson H (1992) Initial experience with V. berus specific Fab antivenom. Proceedings of the XV European Association of Poison Centres and Clinical Toxicology Congress, Istanbul, 1992 (abstr)

    Google Scholar 

  • Pond SM, Pentel PR, Keyler DE, Winzor DJ (1991) Determination of the in-vivo antigen-antibody affinity constant from the redistribution of desipramine specific monoclonal antibody. Biochem Pharmacol 41(3): 473–476

    Article  PubMed  CAS  Google Scholar 

  • Rabetoy GM, Price CA, Findlay JWA, Sailstad JM (1990) Treatment of digoxin intoxication in a renal failure patient with digoxin specific antibody fragments and plasmapheresis. Am J Nephrol 10: 518–521

    Article  PubMed  CAS  Google Scholar 

  • Sabouraud A, Denis H, Urtizberea M, Chappey O, Scherrmann J-M (1990) The effect of nortriptyline-specific active immunization on amitriptyline toxicity and disposition in the rabbit. Toxicology 62(3): 349–360

    Article  PubMed  CAS  Google Scholar 

  • Sabouraud A, Urtizberea M, Grandgeorge JM, Gattel P, Makula MF, Scherrmann J-M (1991) Dose-dependent reversal of acute murine colchicine intoxication by specific goat anti-colchicine Fab fragments. Toxicology 68: 121–132

    Article  PubMed  CAS  Google Scholar 

  • Sabouraud AE, Urtizberea M, Cano NJ, Grandgeorge JM, Rouzioux M, Scherrmann J-M (1992a) Colchicine specific Fab fragments alter colchicine disposition in rabbits. J Pharmacol Exp Ther 260(3): 1214–1219

    PubMed  CAS  Google Scholar 

  • Sabouraud AE, Urtizberea M, Benmoussa K, Cano NJ, Scherrmann J-M (1992b) Fab bound colchicine appears to adopt Fab fragment disposition in rats. J Pharm Pharmacol 44: 1015–1019

    Article  PubMed  CAS  Google Scholar 

  • Sabouraud A, Urtizberea M, Scherrmann J-M, Caraux J, Baud F, Bismuth C (1992c) First pharmacokinetic investigation of colchicine specific Fab fragments in one case of human colchicine poisoning. Proceedings of the XV European Association of Poison Centres and Clinical Toxicology Congress, Istanbul, 1992

    Google Scholar 

  • Schaumann W, Kaufmann B, Neubert P, Smolarz A (1986) Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Eur J Clin Pharmacol 30: 527–533

    Article  PubMed  CAS  Google Scholar 

  • Shumiak GM, Wu AW, Ping AC (1988) Oleander poisoning. Treatment with digoxin specific Fab antibody fragments. Ann Emerg Med 17: 732–735

    Article  Google Scholar 

  • Sinclair AJ, Hewick DS, Johnston PC, Stevenson IH, Lemon M (1989) Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity. Br J Clin Pharmacol 28: 352–356

    PubMed  CAS  Google Scholar 

  • Smith TW (1988) Digitalis: Mechanisms of action and clinical use. N Engl J Med 318: 358–365

    Article  PubMed  CAS  Google Scholar 

  • Smith TW, Haber E (1970) Digoxin intoxication: The relationship of clinical presentation to serum digoxin concentration. J Clin Invest 49: 2377–2386

    Article  PubMed  CAS  Google Scholar 

  • Smith TW, Butler VP, Haber E et al. (1982) Treatment of life threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Experience in 26 cases. N Engl J Med 307: 1357–1362

    Article  PubMed  CAS  Google Scholar 

  • Smith TW, Haber TE, Yeatman L, Butler VP Jr (1976) Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med 294: 797–800

    Article  PubMed  CAS  Google Scholar 

  • Smolarz A, Roesch E, Lenz H, Neubert P, Abshagen U (1984) Erfahrungsbericht ĂĽber die Behandlung von 16 schweren Glykosidvergiftungen mit digitalis-antikorper-Fragmenten (Fab). Z Kardiol 73(2): 113–119

    PubMed  CAS  Google Scholar 

  • Sullivan JB (1986) Immunotherapy in the poisoned patient. Overview of present applications and future trends. Med Toxicol 1: 47–60

    PubMed  Google Scholar 

  • Terrien N, Urtizberea M, Scherrmann JM (1990) Reversal of advanced colchicine toxicity in mice with goat colchicine-specific antibodies. Toxicol Appl Pharmacol 104(3): 504–510

    Article  PubMed  CAS  Google Scholar 

  • Ujhelyi MR, Colucci RD, Cummings DM et al. (1991) Monitoring serum digoxin concentrations during digoxin immune Fab therapy. Drug Intell Clin Pharm 25: 1047–1049

    CAS  Google Scholar 

  • Ujhelyi MR, Cummings DM, Green PJ, Robert S, Vlasses PH, Zarowitz BJ (1992) Free digoxin concentrations using three immunoassay methods in patients receiving digoxin Fab antibodies. 92nd Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, San Antonio. Clin Pharm Ther 49(2): 131

    Google Scholar 

  • Wenger TL (1991) Experience with digoxin immune Fab (ovine) in patients with renal impairment. Am J Emerg Med 9 (suppl 1): 21–23

    Article  PubMed  CAS  Google Scholar 

  • Wieland JM, Marchlinski FE (1986) Electrocardiographic response of digoxin toxic fascicular tachycardia to Fab fragments: Implications for tachycardia mechanism. PACE 9: 727–738

    PubMed  CAS  Google Scholar 

  • Woolf AD, Wenger T, Smith TW, Love joy FH (1992) The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med 326: 1739–1744

    Article  PubMed  CAS  Google Scholar 

  • Zucker AR, Lacina SJ, DasGupta DS et al. (1982) Fab fragments of digoxin specific antibodies used to reverse ventricular fibrillation induced by digoxin ingestion in a child. Pediatrics 70(3): 468–471

    PubMed  CAS  Google Scholar 

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  1. A. J. Heath
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Editors and Affiliations

  1. Department of Chemical Pathology, St Bartholomew’s Hospital Medical College, Charterhouse Square, London, EC1M 7BQ, UK

    John Landon MD, FRCP

  2. Joint Academic Unit of Obstetrics, Gynaecology and Reproductive Physiology, St Bartholomew’s Hospital Medical College, West Smithfield, London, EC1A 7BE, UK

    Tim Chard MD, FRCOG

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© 1995 Springer-Verlag London Limited

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Heath, A.J. (1995). Immunotherapy for Drug Toxicity. In: Landon, J., Chard, T. (eds) Therapeutic Antibodies. Springer, London. https://doi.org/10.1007/978-1-4471-1937-1_5

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  • DOI: https://doi.org/10.1007/978-1-4471-1937-1_5

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-1939-5

  • Online ISBN: 978-1-4471-1937-1

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