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Vol. 292, Issue 3, 831-837, March 2000
Departments of Pharmacology and Toxicology (J.W.P., S.M.O.) and
Anesthesiology (W.B.G.), College of Medicine, University of Arkansas
for Medical Sciences, Little Rock, Arkansas
These studies examined the hypothesis that a single large dose of
monoclonal anti-phencyclidine (PCP) antibody could provide long-term
reductions in brain PCP concentrations despite continuous PCP
administration. PCP (18 mg/kg/day, s.c.) was infused to steady-state (24 h) and then a mole-equivalent dose of a short-acting anti-PCP antigen-binding fragment (Fab) or a long-acting anti-PCP IgG was administered i.v. The PCP infusion continued for up to 27 days, even
though the binding capacity of the single dose of antibody used should
have been saturated within the first day. At selected time points after
antibody administration, brain, testis, and serum PCP concentrations
were measured. Serum PCP concentrations rapidly increased ~100- and
300-fold after Fab or IgG administration, respectively. Based on the
antibody-bound PCP concentrations in serum, the functional elimination
half-life (t1/2
Z) values for PCP-Fab and
PCP-IgG complexes were 9.4 h and 15.4 days, respectively. Fab and
IgG administration produced a complete removal of PCP from the brain
within 15 min. Although brain PCP concentrations were significantly
decreased for only 4 h in Fab-treated animals, IgG administration
resulted in significant decreases in brain PCP concentrations lasting
for at least 27 days. In contrast, testis PCP concentrations were not
substantially affected by antibody administration, suggesting that
redistribution of PCP from the testis is too slow to benefit from a
limited dose of antibody. These results indicate that anti-PCP IgG can
preferentially protect the brain for ~4 weeks after IgG
administration, even when the antibody binding capacity should have
been saturated with continuously administered PCP.
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