Anti-phencyclidine monoclonal antibodies provide long-term reductions in brain phencyclidine concentrations during chronic phencyclidine administration in rats

These studies examined the hypothesis that a single large dose of monoclona l anti-phencyclidine (PCP) antibody could provide long-term reductions in b rain PCP concentrations despite continuous PCP administration. PCP (18 mg/k g/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-ac ting anti-PCP IgG was administered i.v. The PCP infusion continued for up t o 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 poin ts after antibody administration, brain, testis, and serum PCP concentratio ns were measured. Serum PCP concentrations rapidly increased similar to 100 - and 300-fold after Fab or IgG administration, respectively. Based on the antibody-bound PCP concentrations in serum, the functional elimination half -life (t(1/2 lambda Z)) values for PCP-Fab and PCP-IgG complexes were 9.4 h and 15.4 days, respectively. Fab and IgG administration produced a complet e removal of PCP from the brain within 15 min. Although brain PCP concentra tions were significantly decreased for only 4 h in Fab-treated animals, IgG administration resulted in significant decreases in brain PCP concentratio ns lasting for at least 27 days. In contrast, testis PCP concentrations wer e not substantially affected by antibody administration, suggesting that re distribution of PCP from the testis is too slow to benefit from a limited d ose of antibody. These results indicate that anti-PCP IgG can preferentiall y protect the brain for;4 weeks after IgG administration, even when the ant ibody binding capacity should have been saturated with continuously adminis tered PCP.