Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs

S. M. Owens, Michael Mayersohn

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalDrug Metabolism and Disposition
Volume14
Issue number1
StatePublished - 1986

Fingerprint

Phencyclidine
Immunoglobulin Fab Fragments
Dogs
Antibody Affinity
Plasmas
Protein Binding
Goats
Blood
Pharmaceutical Preparations
Dialysis
Pharmacokinetics
Erythrocytes
Kidney
Antigens
Metabolites
Toxicity
Serum
Cells
Antibodies

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 journalArticle

@article{f375e7925e3f400e8c147a38ff8ffd46,
title = "Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs",
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.",
author = "Owens, {S. M.} and Michael Mayersohn",
year = "1986",
language = "English (US)",
volume = "14",
pages = "52--58",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0022598189&partnerID=8YFLogxK

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 -