Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs.
High affinity antibodies (K0 = 3 X 10(9) M-1) against the widely abused drug phencyclidine (PCP) were produced in goats and then purified and extensively characterized for use in in vivo pharmacokinetic studies. An iv dose of 3H-PCP was administered to three dogs, followed 2 hr later by an equimolar dose of PCP-specific antigen-binding fragments (Fab). Within 10 min after Fab administration, the concentration of PCP in the serum had increased 17-56-fold in the three dogs. The Fab administration also produced a 10-fold decrease in volume of distribution and in systemic and renal clearances. The concentration of PCP metabolites decreased for a period of time after Fab administration. Equilibrium dialysis studies showed that the percentage of unbound PCP changed from about 50% before Fab administration to less than 1% unbound after Fab. In addition, the blood/plasma ratio of PCP changed from a near-equal distribution between red blood cells and plasma before Fab to virtually all of the drug being confined to the plasma fraction after Fab administration. Although Fab produced a dramatic redistribution and extensive protein binding of PCP, the route of elimination of PCP was not altered. These data suggest that high affinity anti-PCP Fab could reverse the toxicity of PCP.
Owens
S M
SM
Mayersohn
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D000818:Animals; D003429:Cross Reactions; D004285:Dogs; D006041:Goats / Q000276:immunology; D006207:Half-Life; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D010622:Phencyclidine / Q000276:immunology / Q000378:metabolism*
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010622:Phencyclidine