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 scorpion antivenom and its effect on Buthus occitanus mardochei venom plasma disposition in the rabbit were studied. The scorpion venom-specific F(ab')2 affinity constant determined by immunoradiometric assay was 1.6 +/- 0.6 10(8) M-1. One group received a F(ab')2 bolus dose of 9.57 mg.kg-1 i.v. bolus or i.m.. The plasma F(ab')2 concentration followed a biexponential decline after i.v. administration with distribution and elimination half-lives of 2.54 +/- 0.36 and 49.52 +/- 3.07 hr, respectively. The total volume of distribution (Vdss or Vd beta) was between 230 and 255 ml.kg-1. Total body clearance was 3.56 +/- 0.34 ml.kg-1.hr-1. After intramuscular administration, Tmax was 48 hr and the absolute bioavailability was 36%. Two other groups of rabbits received i.v.60 micrograms.kg-1 B. occitanus mardochei venom either alone (control group) or followed by 3 mg.kg-1 scorpion venom-specific F(ab')2 administered by intravenous infusion 1.75 hr later. 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 administration. Subsequent infusion of antivenom induced a 1.5-fold elevation of the plasma venom concentration with a Tmax 0.5 hr after F(ab')2 administration. 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. Twelve 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 hr). These data show the ability of F(ab')2 to alter venom pharmacokinetics and demonstrate that the scorpion toxins adopt the F(ab')2 elimination properties.
Pépin-Covatta
S
S
Institut National de la Santé et de la Recherche Médicale, U26, Hôpital Fernand Widal, Paris, France.
Lutsch
C
C
Grandgeorge
M
M
Lang
J
J
Scherrmann
J M
JM
D000818:Animals; D000997:Antivenins / Q000276:immunology / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D004347:Drug Interactions; D006207:Half-Life; D006736:Horses; D015592:Immunoradiometric Assay; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011817:Rabbits; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors* / Q000276:immunology; D014018:Tissue Distribution
D000997:Antivenins; D012604:Scorpion Venoms