Pharmacokinetics of 125I-labelled IgG, F(ab')2 and Fab fractions of scorpion and snake antivenins: merits and potential for therapeutic use.
The immunoglobulin fractions IgG, F(ab')2 and Fab of scorpion and snake antivenoms possess pharmacokinetic characteristics that are significantly different from their respective venoms. The venoms (and their toxins) are several fold faster in their distribution into the tissues than any of the immunoglobulin fraction. In rabbits, F(ab')2 possessed the fastest disposition rate constants and the longest distribution half lives. In the physiologically based pharmacokinetic experiments carried out in mice F(ab')2 possessed the highest Cp(max), smallest AUC and the shortest t1/2beta in the different tissues while Fab had values in between IgG and F(ab')2. Rescue experiments in anaesthetized rats challenged with lethal doses of venoms or toxins and infused with border-line neutralizing doses of antivenoms, showed that rats infused with F(ab')2 completely recovered, those infused with IgG partially rescued and none of the rats infused with Fab survived. It is concluded that F(ab')2 of scorpion and snake antivenoms possess pharmacokinetic characteristics that render it the most suitable for use in serotherapy of scorpion and snake envenoming.
Ismail
M
M
The Antivenom and Vaccine Production Centre, King Fahad National Guard Hospital, Riyadh, Saudi Arabia.
Abd-Elsalam
M A
MA
D000818:Animals; D000997:Antivenins / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D004546:Elapid Venoms / Q000276:immunology*; D017815:Elapidae; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D051379:Mice; D011817:Rabbits; D051381:Rats; D065008:Scorpion Stings / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D012604:Scorpion Venoms / Q000276:immunology*; D012605:Scorpions; D012909:Snake Bites / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D014018:Tissue Distribution
D000997:Antivenins; D004546:Elapid Venoms; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D012604:Scorpion Venoms