Annals of Emergency Medicine
Volume 37, Issue 2 , Pages 189-195 , February 2001

Recurrence phenomena after immunoglobulin therapy for snake envenomations: part 1. Pharmacokinetics and pharmacodynamics of immunoglobulin antivenoms and related antibodies

Presented at the North American Congress of Clinical Toxicology’s “Advances in the Management of Snakebite” Symposium, October 1999, La Jolla, CA.

Received 20 October 1999 ,Revised 31 October 2000 ,Accepted 1 December 2000.

References 

  1. Smith TW, Lloyd BI, Spicer N, et al.  Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon. Clin Exp Immunol. 1979;36:384–396
  2. Smith DC, Reddi KR, Laing G, et al.  An affinity purified ovine antivenom for the treatment of Vipera berus envenoming. Toxicon. 1992;30:865–871
  3. Seifert SA, Boyer LV, Dart RC, et al.  Relationship of venom effects to venom antigen and antivenom serum concentrations in a patient with Crotalus atrox enevenomation treated with a Fab antivenom. Ann Emerg Med. 1997;30:49–53
  4. Seifert SA, Dart RC, Bogdan GM, et al.  Recurrence of local symptoms of crotalid envenomation in ovine Fab antivenom treated patients [abstract]. J Toxicol Clin Toxicol. 1999;37:390
  5. Seifert SA, Dart RC, Boyer LV, et al.  Prevention and Treatment of recurrent local symptoms in crotalid envenomation treated with ovine Fab [abstract]. J Toxicol Clin Toxicol. 1999;37:668
  6. Boyer LV, Seifert SA, Clark RF, et al.  Recurrent and persistent coagulopathy following pit viper envenomation. Arch Intern Med. 1999;159:706–710
  7. Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity. Clin Pharmacokinet. 1995;28:483–493
  8. Ho M, Silamut K, White N, et al.  Pharmacokinetics of three commercial antivenoms in patients envenomed by the malayan pit viper, Calloselasma rhodostoma, in Thailand. Am J Trop Med Hyg. 1990;42:260–266
  9. Hardy DL, Monette J, Corrigan JJ. Envenomation by the northern blacktail rattlesnake (Crotalus molossus molossus): report of two cases and the in vitro effects of the venom on fibrinolysis and platelet aggregation. Toxicon. 1982;20:487–493
  10. Meyer WP, Habib AG, Onayade AA, et al.  First clinical experiences with a new ovine Fab' Echis ocellatus snake bite antivenom in Nigeria: randomized comparative trial with Institute Pasteur serum (IPSER) Africa antivenom. Am J Trop Med Hyg. 1997;56:291–300
  11. Azuma J, Kurimoto T, Tsuji S, et al.  Phase I study on human monoclonal antibody against cytomegalovirus: pharmacokinetics and immunogenicity. J Immunother. 1991;10:278–285
  12. Covell DG, Barbet J, Holton OD, et al.  Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice. Cancer Res. 1986;46:3969–3978
  13. Schaumann W, Kaufmann B, Neubert P, et al.  Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Eur J Clin Pharmacol. 1986;30:527–533
  14. Pepin S, Lutsch C, Grandgeorge M, et al.  Snake F(ab')2 antivenom from hyperimmunized horse: pharmacokinetics following intravenous and intramuscular administrations in rabbits. Pharm Res. 1995;12:1470–1473
  15. Lloyd BL, Smith TW. Contrasting rates of reversal of digoxin toxicity by digoxin-specific IgG and Fab' fragments. Circulation. 1978;58:280–283
  16. Wochner RD, Strober W, Waldman TA. The role of the kidney in the catabolism of Bence-Jones proteins and immunoglobin fragments. J Exp Med. 1967;126:207–221
  17. Bazin-Redureau MI, Renard CB, Scherrmann J-MG. Pharmacokinetics of heterologous and homologous immunoglobulin G, F(ab')2 and Fab after intravenous administration in the rat. J Pharm Pharmacol. 1997;49:277–281
  18. Chang RS, Ueki IF, Troy JL, et al.  Permselectivity of the glomerular capillary wall to macromolecules. II. Experimental studies in rat using neutral dextran. Biophys J. 1975;15:887–906
  19. Arend WP, Silverblatt FJ. Serum disappearance and catabolism of homologous immunoglobulin fragments in rats. Clin Exp Immunol. 1975;22:502–513
  20. Pentel PR, Keyler DE, Gilbertson DG, et al.  Pharmacokinetics and toxicity of high doses of antibody Fab fragments in rats. Drug Metab Dispos. 1988;16:141–145
  21. Rennke HG, Patel Y, Venkatachalam MA. Glomerular filtration of proteins: clearance of anionic, neutral, and cationic horseradish peroxidase in the rat. Kidney Int. 1978;13:278–288
  22. Bertolatus JA, Hunsicker LG. Glomerular sieving of anionic and neutral bovine albumins in proteinuric rats. Kidney Int. 1985;28:467–476
  23. Gillissen A, Theakston RDG, Barth J, et al.  Neurotoxicity haemostatic disturbances and haemolytic anaemia after a bite by a Tunisian saw-scaled or carpet viper (Echis ‘pyramidum’ -complex): failure of antivenom treatment. Toxicon. 1994;32:937–944
  24. Sorensen HNH, Faber V, Svehag SE. Circulating immune complexes, complement activation kinetics and serum sickness following treatment with heterologous anti-snake venom globulin. Scand J Immunol. 1978;7:25–33
  25. Ownby CL, Reisbeck SL, Allen R. Levels of therapeutic antivenin and venom in a human snakebite victim. South Med J. 1996;89:803–806
  26. Iwanaga S, Suzuki T. Enzymes in snake venom. In:  Lee C-Y editors. Snake Venoms. Berlin: : Springer Verlag; 1979;p. 64–65
  27. Owens SM, Mayersohn M. Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs. Drug Metab. 1986;14:52–58
  28. Humphreys DP, Vetterlein OM, Chapman AP, et al.  F(ab')2 molecules made from Escherichia coli produced Fab' with hinge sequences conferring increased serum survival in an animal model. J Immunol Methods. 1998;217:1–10
  29. Lomonte B, Leon G, Hanson LA. Similar effectiveness of Fab' and F(ab')2 antivenoms in the neutralization of hemorrhagic activity of Vipera berus snake venom in mice. Toxicon. 1996;34:1197–1202
  30. Gutierrez JM, Leon G, Rojas G, et al.  Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom. Toxicon. 1998;36:1529–1538
  31. Chatenoud L. Humoral immune response against OKT3. Transplant Proc. 1993;25(2 Suppl 1):68–73
  32. Dart RC, Seifert SA, Carroll L, et al.  Human trial of an affinity purified antibody fragment for snake venom poisoning [abstract]. Vet Human Toxicol. 1994;36:363
  33. Seifert SA. Pharmacokinetic analysis of a crotalid Fab antivenom and theoretical considerations for the prevention of coagulopathic recurrence [abstract]. J Toxicol Clin Toxicol. 1998;36:526–527
  34. Seifert SA. Pharmacokinetic analysis of a crotalid Fab antivenom and theoretical considerations for the prevention of coagulopathic recurrence. Presented at the North American Congress of Clinical Toxicology, September 15, 1998; Orlando, FL.
  35. Bajwa SS, Markland FS, Russell FE. Fibrinolytic enzyme(s) in Western diamondback rattlesnake (Crotalus atrox) venom. Toxicon. 1980;18:285–290
  36. Ouyang C, Teng C-M, Huang T-F. Characterization of snake venom components acting on blood coagulation and platelet function. Toxicon. 1992;30:945–966
  37. Hasiba U, Rosenbach LM, Rockwell D, et al.  DIC-like syndrome after envenomation by the snake, Crotalus horridus horridus. N Engl J Med. 1975;292:505–507
  38. Furlow TG, Brennan LV. Purpura following timber rattlesnake (Crotalus horridus horridus) envenomation. Cutis. 1985;35:234–236
  39. Lyons WJ. Profound thrombocytopenia associated with Crotalus ruber ruber envenomation: a clinical case. Toxicon. 1971;9:237–240
  40. Budzynski AZ, Pandya BV, Rubin RN, et al.  Fibrinogenolytic afibrinogenemia after envenomation by Western diamondback rattlesnake (Crotalus atrox). Blood. 1984;63:1–14
  41. Tallon RW, Kock KL, Barnes SG, et al.  Envenomation coagulopathy from snakebites [letter]. N Engl J Med. 1981;305:1347
  42. La Grange E, Russell FE. Blood platelet studies in man and rabbits following Crotalus envenomation. Proc West Pharm Soc. 1970;13:99–105
  43. Pepin-Covatta S, Lutsch C, Lang J, et al.  Preclinical assessment of immunoreactivity of a new purified equine F(ab')2 against European viper venom. J Pharmaceut Sci. 1998;87:221–225
  44. Kobayashi H, Le N, Kim I, et al.  The pharmacokinetic characteristic of glycolated humanized anti-Tac Fab' are determine by their isoelectric points. Cancer Res. 1999;59:422–430
  45. Fagnani R, Halpern S, Hagan M. Altered pharmacokinetic and tumour localization properties of Fab' fragments of a murine monoclonal anti-CEA antibody by covalent modification with low molecular weight dextran. Nucl Med Comm. 1995;16:269–362
  46. Mordenti J, Chen SA, Moore JA, et al.  Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharmaceut Res. 1991;8:1351–1359
  47. Thanh-Barthet CV, Urtizberea M, Sabouraud AE, et al.  Development of a sensitive radioimmunoassay for Fab fragments: application to Fab pharmacokinetics in humans. Pharm Res. 1993;10:692–695
  48. Allen NM, Dunham GD, Sailstad JM, et al.  Clinical and pharmacokinetic profiles of digoxin immune Fab in four patients with renal impairment. DICP. 1991;25:1315–1320
  49. Caspi O, Zylber-Katz E, Gotsman O, et al.  Digoxin intoxication in a patient with end-stage renal disease: efficiency of digoxin-specific Fab antibody fragments and peritoneal dialysis. Ther Drug Monit. 1997;19:510–515

 Supported in part by Altana, Inc.

☆☆ Address for reprints: Steven A. Seifert, MD, Leslie V. Boyer, MD, c/o Arizona Poison and Drug Information Center, 1501 North Campbell Avenue, Tucson, AZ 85724; 520-626-7899, fax 520-626-2720; E-mail sseifert@pol.net .

PII: S0196-0644(01)54163-3

doi: 10.1067/mem.2001.113135

Annals of Emergency Medicine
Volume 37, Issue 2 , Pages 189-195 , February 2001