Abstract
High affinity antibodies (K0 = 3 x 109 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 <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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 52-58 |
| Number of pages | 7 |
| Journal | Drug Metabolism and Disposition |
| Volume | 14 |
| Issue number | 1 |
| State | Published - 1986 |
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ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs. / Owens, S. M.; Mayersohn, Michael.
In: Drug Metabolism and Disposition, Vol. 14, No. 1, 1986, p. 52-58.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs
AU - Owens, S. M.
AU - Mayersohn, Michael
PY - 1986
Y1 - 1986
N2 - High affinity antibodies (K0 = 3 x 109 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 <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.
AB - High affinity antibodies (K0 = 3 x 109 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 <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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0022598189&partnerID=8YFLogxK
M3 - Article
C2 - 2868866
AN - SCOPUS:0022598189
VL - 14
SP - 52
EP - 58
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 1
ER -