Snake F(ab')2 antivenom from hyperimmunized horse: pharmacokinetics following intravenous and intramuscular administrations in rabbits.

Abstract

The pharmacokinetics of a currently available horse F(ab')2 antivenoms to Vipera aspis, V. ammodytes, and V. berus (Ipser Europe) and a new more purified and pasteurized preparation (SAV) was investigated in the rabbit. An immunoradiometric assay using an affinity-purified goat IgG horse F(ab')2 specific and the same IgG labelled with iodine 125 as a tracer was developed. The limit of quantification in plasma was 0.032 microgram/ml. Specificity study showed that mouse F(ab')2 and Fab did not cross-react. Pharmacokinetic analysis showed that the plasma F(ab')2 concentration followed a biexponential decline after intravenous bolus administration with distribution and elimination half-lives of 2.66 +/- 0.18 hrs and 49.69 +/- 4.13 hrs, respectively. The total volume of distribution (Vdss or Vd beta) was between 209 and 265 ml.kg-1 and was similar to the volume of the extracellular fluid in the rabbit (300 ml.kg-1). Total body clearance ranged from 3.33 to 3.96 ml.h-1.kg-1. After intramuscular administration which was only investigated with SAV, Tmax was 48 hrs and the absolute bioavailability was 42%. No difference in pharmacokinetics was observed between the two antivenom preparations following the intravenous administration. In contrast, a reduced rate and extent of absorption was shown following intramuscular administration.