IMMUNOREACTIVITY AND PHARMACOKINETICS OF HORSE ANTI-SCORPION VENOM F(AB')(2)-SCORPION VENOM INTERACTIONS

The immunoreactivity and pharmacokinetics of a new horse F(ab')(2) sco rpion antivenom and its effect on Buthus occitanus mardochei venom pla sma disposition in the rabbit were studied. The scorpion venom-specifi c F(ab')(2) affinity constant determined by immunoradiometric assay wa s 1.6 +/- 0.6 10(8) M(-1). One group received a F(ab')(2) bolus dose o f 9.57 mg . kg(-1) i.v. bolus or i.m.. The plasma F(ab')(2) concentrat ion followed a biexponential decline after i.v. administration with di stribution and elimination half-lives of 2.54 +/- 0.36 and 49.52 +/- 3 .07 hr, respectively, The total volume of distribution (Vdss or Vd bet a) was between 230 and 255 ml . kg(-1). Total body clearance was 3.56 +/- 0.34 ml . kg(-1). hr(-1). After intramuscular administration, T-ma x was 48 hr and the absolute bioavailability was 36%. Two other groups of rabbits received i.v. 60 mu g . kg(-1) B. occitanus mardochei veno m either alone (control group) or followed by 3 mg . kg(-1) scorpion v enom-specific F(ab')(2) administered by intravenous infusion 1.75 hr l ater. In the rabbits treated with horse F(ab')(2) antivenom the venom concentration profile was initially identical to that observed in the control group which received venom alone before F(ab')(2) administrati on, Subsequent infusion of antivenom induced a 1.5-fold elevation of t he plasma venom concentration with a T-max 0.5 hr after F(ab')(2) admi nistration, The AUC was 10-fold higher in the F(ab')(2)-treated group than in the control group in the post-F(ab')(2) infusion period, Twelv e hours after F(ab')(2) administration the venom disposition declined with a terminal half-life equal to that of F(ab')(2) (49.49 +/- 7.53 h r). These data show the ability of F(ab')(2) to alter venom pharmacoki netics and demonstrate that the scorpion toxins adopt the F(ab')(2) el imination properties. (C) 1996 Academic Press, Inc.