SNAKE F(AB')(2) ANTIVENOM FROM HYPERIMMUNIZED HORSE - PHARMACOKINETICS FOLLOWING INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATIONS IN RABBITS

Purpose. The pharmacokinetics of a currently available horse F(ab')(2) antivenoms to Vipera aspis, V. ammodytes, and V. bents (Ipser Europe) and a new more purified and pasteurized preparation (SAV) was investi gated in the rabbit. Methods. An immunoradiometric assay using an affi nity-purified goat IgG horse F(ab')(2) specific and the same IgG label led with iodine 125 as a tracer was developed. The limit of quantifica tion in plasma was 0.032 mu g/ml. Specificity study showed that mouse F(ab')(2) and Fab did not cross-react. Results. Pharmacokinetic analys is showed that the plasma F(ab')(2) concentration followed a biexponen tial 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 ex tracellular 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 admini stration which was only investigated with SAV, Tmax was 48 hrs and the absolute bioavailability was 42%. Conclusions. No difference in pharm acokinetics was observed between the two antivenom preparations follow ing the intravenous administration. In contrast, a reduced rate and ex tent of absorption was shown following intramuscular administration.