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 mod el using a specific sandwich type ELISA. After intravenous injection, Bot v enom seems to follow a three-compartment pharmacokinetic open model. Howeve r, after subcutaneous injection, the distribution and elimination kinetics of Bot venom are best characterized by a bi-compartment pharmacokinetic ope n 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 v enom 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 parameter s and on the antivenom immunotherapy efficacy were then studied. These stud ies indicated in particular that: (1) the injection of a minimal neutralizi ng antivenom dose is required for a complete and permanent neutralization o f circulating venom antigens; this dose is named minimal (threshold) effica cious antivenom dose; (2) the intramuscular route is not the most appropria te way for antivenom injection; and (3) a delayed antivenom immunotherapy r emains efficacious especially on the neutralization of the remaining circul ating venom. In short, these experimental studies show that early intraveno us injection of an appropriate antivenom dose (at least the threshold effic acious dose) is the indicated way for a rapid and permanent neutralization of circulating scorpion Venom toxins. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.