Preclinical assessment of immunoreactivity of a new purified equine F(ab')2 against European viper venom.
The immunological and pharmacokinetic properties of a new, further purified, pasteurized preparation of equine F(ab')2 (VIPERFAV) against Vipera aspis, Vipera berus, and Vipera ammodytes venom were compared with the current equine F(ab')2 preparation (IPSER Europe). Affinity constants of the V. aspis-specific F(ab')2 were determined using biosensor technology and found to be in the range of 10(8) M-1 for the four antigenic fractions of V. aspis toxins and for both F(ab')2 preparations. The improvement of 51% in the specific activity (LD50 mg-1) of the new F(ab')2 was in close agreement with the 1.8-fold increase in the immunoreactive fraction of the new preparation. In vivo investigations of venom immunocomplexation by F(ab')2 in rabbits confirmed the ability of F(ab')2 to neutralize and redistribute toxin venom. Infusion of a stoichiometric molar ratio (i.e., 1 mg kg-1) of the new antivenom induced a 2.3-fold elevation of the plasma venom concentration with a Tmax observed 8 h after F(ab')2 administration and a decline in the terminal half-life from 31.92 +/- 4.49 h to 16.73 +/- 4.34 h, in contrast, for the venom alone. The area under the curve was 1.4-fold greater in the VIPERFAV group than in the IPSER Europe group during the post-F(ab')2 infusion period. Increasing the F(ab')2 dose to 3 mg kg-1 increased by 27% the percent of venom bound to F(ab')2. Finally, the greater the venom distribution, the smaller and less pronounced the plasma redistribution. These results demonstrate that the purification and pasteurization steps involved in the preparation of the new F(ab')2 have no deleterious influence on F(ab')2 affinity but, on the contrary, improve the protective efficacy. Alteration of viper venom kinetics by specific F(ab')2 antivenom was also shown to be dependent on the interval between of F(ab')2 administration and venom bite and on the specific F(ab')2 dose administered.
Pepin-Covatta
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S
Institut National de la Santé et de la Recherche Médicale, U26, Hôpital Fernand Widal, Paris, France.
Lutsch
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C
Lang
J
J
Scherrmann
J M
JM
D000818:Animals; D000997:Antivenins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D019540:Area Under Curve; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007262:Infusions, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011817:Rabbits; D014757:Viper Venoms / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000493:pharmacokinetics
D000997:Antivenins; D007140:Immunoglobulin Fab Fragments; D014757:Viper Venoms