Pharmacokinetics of 125I-labelled antivenin to the venom from the scorpion Androctonus amoreuxi

Abstract

An antivenin for A. amoreuxi venom was prepared by hyperimmunizing rabbits. The globulin fraction was separated and purified and the immunogloblin fraction (chiefly IgG) separated, purified and radioiodinated. Using the immunodifussion technique, seven prominent and two faint precipitin bands were found with both the crude antivenin and the globulin fraction and four prominent and one faint precipitin bands with the immunoglobulin fraction, when tested against the venom. Ten milligrams of the immunoglobulin fraction (Ig) protected the mice from the lethal action of a dose of the venom equal to 5 times the ld 50. The corresponding values for the globulin fraction and the crude antivenin were 70 mg and 4 ml, respectively. The pharmacokinetic profile of the labelled Ig was determined following rapid i.v. injection into rabbits. The data obtained showed an excellent fit to a triexponential equation of the form: C p,t= Pe − πt + Ae − αt ;+ Be − βt ; where C p,t is the antivenin concentration in the blood at time t, π, α and β are hybrid rate constants and P, A and B are the corresponding zero time intercepts. This equation represents a pharmacokinetic model consisting of a central compartment from which distribution to a rapidly equilibrating “shallow” compartment and a slowly equilibrating “deep” compartment takes place, with elimination taking place from the central compartment. The apparent half-lives for the early declining phases were 1.06 and 9.63 hr for the rapidly and slowly equilibrating compartments, respectively. The overall elimination half life was 43.3 hr. The ineffectiveness of serotherapy with scorpion antiven injected several hours after scorpion sting might be due to differences in distribution half lives.