Effects of antivenom on Buthus occitanus tunetanus (Bot) scorpion venom pharmacokinetics: towards an optimization of antivenom immunotherapy in a rabbit model.

The pharmacokinetic parameters of Bot venom were determined in a rabbit model using a specific sandwich type ELISA. After intravenous injection, Bot venom seems to follow a three-compartment pharmacokinetic open model. However, after subcutaneous injection, the distribution and elimination kinetics of Bot venom are best characterized by a bi-compartment pharmacokinetic open model. Bot venom is completely absorbed from its SC injection site, since the absolute bioavailability is higher than 95%; the maximum plasma venom concentration is reached between 30 and 60 min after venom injection. Bot venom diffuses rapidly to tissues and is distributed in a high body volume. The total body clearance of Bot venom is relatively high in agreement with a low mean residence time. Antivenom immunotherapy experiments were carried out in the rabbit model, in order to select the most appropriate strategy for the adequate use of this treatment. The effects of the route, the dose and the delay of antivenom injection on Bot venom pharmacokinetic parameters and on the antivenom immunotherapy efficacy were then studied. These studies indicated in particular that: (1) the injection of a minimal neutralizing antivenom dose is required for a complete and permanent neutralization of circulating venom antigens; this dose is named minimal (threshold) efficacious antivenom dose; (2) the intramuscular route is not the most appropriate way for antivenom injection; and (3) a delayed antivenom immunotherapy remains efficacious especially on the neutralization of the remaining circulating venom. In short, these experimental studies show that early intravenous injection of an appropriate antivenom dose (at least the threshold efficacious dose) is the indicated way for a rapid and permanent neutralization of circulating scorpion venom toxins.