Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in rats: optimization of antivenom therapy.
This paper reports the simultaneous determination of toxicokinetic and toxicodynamic properties of Androctonus australis hector venom, in the absence and presence of antivenom (F(ab')(2) and Fab), in envenomed rats. After subcutaneous injection of the venom, toxins showed a complete absorption phase from the site of injection associated with a distribution into a large extravascular compartment. The injection of Fab and F(ab')(2) induced the neutralization of venom antigens in the blood compartment, as well as the redistribution of venom components from the extravascular compartment to the blood compartment. Interestingly, F(ab')(2) and Fab showed distinct efficiencies depending on their route of injection. F(ab')(2) induced a faster venom neutralization and redistribution than Fab when injected intravenously. Fab was more effective than F(ab')(2) by the intramuscular route. The hemodynamic effects of Aah venom were further investigated. Changes in mean arterial pressure and heart rate were observed in parallel with an upper airway obstruction. Fab was more effective than F(ab')(2) for preventing early symptoms of envenomation, whatever their route of administration. Intraperitoneal injection of F(ab')(2) and Fab was similar for the prevention of the delayed symptoms, even after a late administration. Fab was more effective than F(ab')(2) in the inhibition of airway resistance, independent of the route and time of administration. These results show that the treatment for scorpion stings might be improved by the intravascular injection of a mixture of Fab and F(ab')(2). If antivenom cannot be administered intravenously, Fab might be an alternative as they are more effective than F(ab')(2) when injected intramuscularly.
Hammoudi-Triki
D
D
Unité des Venins, Institut Pasteur, Paris, France.
Lefort
J
J
Rougeot
C
C
Robbe-Vincent
A
A
Bon
C
C
Laraba-Djebari
F
F
Choumet
V
V
D000402:Airway Obstruction / Q000139:chemically induced / Q000503:physiopathology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000997:Antivenins / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009500:Neutralization Tests; D051381:Rats; D017208:Rats, Wistar; D065008:Scorpion Stings / Q000276:immunology / Q000628:therapy*; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D012605:Scorpions
D000997:Antivenins; D007140:Immunoglobulin Fab Fragments; D012604:Scorpion Venoms