EFFECT OF ANTIVENOM ON VENOM PHARMACOKINETICS IN EXPERIMENTALLY ENVENOMED RABBITS - TOWARD AN OPTIMIZATION OF ANTIVENOM THERAPY

Antivenomous immunotherapy is still used empirically. To improve the e fficacy and safety of immunotherapy, we studied the effects of adminis tering antivenom antibodies (F(ab')(2)) on the pharmacokinetics of the Vipera aspis venom in rabbits. Free venom levels were measured by enz yme-linked immunosorbent assay and total concentrations were quantifie d by measuring the radioactivity of trichloroacetic acid-precipitable radioiodinated venom. The intravenous infusion of 125 mg of antivenom 7 h after intramuscular injection with 700 mu g . kg(-1) of V. aspis v enom produced a redistribution of the venom antigens from the extravas cular to the vascular space. Moreover, antivenom antibodies were able to neutralize the totality of venom antigens in the vascular space, be cause no free plasma venom was detectable by enzyme-linked immunosorbe nt assay within 15 min after antivenom injection. Similar effects were obtained after injection of 25 mg of antivenom; however, the venom wa s only partially neutralized with lower doses (5 and 2.5 mg). We furth er established that intravenous injection is the most efficient route for antivenom administration, and we examined the effects of early and late immunotherapy. Finally, the efficacy of Fab antibodies was compa red with that of F(ab')(2); the plasma redistribution and the immunone utralization of the venom were lower than those induced after injectio n of the same dose of F(ab')(2). The difference between the effects of F(ab')(2) and Fab could be explained by the differential pharmacokine tics of the two fragments.