Pharmacokinetics of the toxic fraction of Centruroides limpidus limpidus venom in in experimentally envenomed rabbits and effects of immunotherapy with specific F(ab ')(2)

Envenomations after scorpion stings are a major health problem throughout t he world. Their specific treatment is immunotherapy which consists of the i njection of specific antibody, In this article, we studied the pharmacokine tics of the toxic fraction of Centruroides limpidus limpidus venom (fractio n II) in experimentally envenomed rabbits, After an intravenous injection, fraction II (FII) was rapidly distributed and eliminated from the body (ter minal half-life of 1.9 h). When injected subcutaneously, high concentration s of FII were measured in the vascular space rapidly after the injection (T -max = 1 h) and FII was eliminated with a terminal half-life of 1.8 h, clos e to that determined after intravenous injection. These observations go alo ng with the rapid onset of clinical symptoms observed after accidental enve nomations. To investigate the mechanism of action of antivenom, we examined the effects of the intravenous administration of antivenom (horse F(ab')(2 ) directed against Centruroides venoms) on the pharmacokinetics of FII. Imm unotherapy performed 2 h after the experimental envenomation largely increa sed the area under the concentration time curve of FII compared to that cal culated in absence of immunotherapy (13,000 versus 170 ng h ml(-1), respect ively). These observations agree with previous findings which showed that s pecific antibody fragments are able to remove drugs from their site of acti on and sequester them in the vascular space. These studies provide a powerf ul tool to determine an excellent procedure for further improvement of immu notherapy. (C) 1999 Science Ltd. All rights reserved.