Antiphencyclidine monoclonal antibody therapy significantly changes phencyclidine concentrations in brain and other tissues in rats.
These studies determined how high-affinity monoclonal antiphencyclidine (PCP) antigen binding fragments of immunoglobulin G (Fab) affects PCP tissue concentrations and serum protein binding in male rats. Animals received an i.v. bolus dose of 1.0 mg/kg of PCP, followed at 2 hr when distribution was complete (but about 70% of the dose remained) by either saline (for controls) or an equimolar dose of anti-PCP Fab. This dose of PCP was chosen because it produces behavioral effects and ataxia for about 40 min. The rats were sacrificed over the next 16 hr (n = 3 per time point) and blood, brain, fat, heart, kidney, liver, lung, muscle and testis were collected. After anti-PCP Fab treatment, serum PCP concentrations increased significantly (P < .05) for the duration of the experiment. This resulted in a decrease in the PCP volume of distribution and systemic clearance to 11 and 12% of controls, respectively. Because these parameters decreased to a similar degree, the terminal elimination half-life was unaltered after Fab treatment. The percentage of unbound PCP in serum averaged 47 +/- 15% (mean +/- S.D.) in controls and 3 +/- 2% in Fab-treated animals for the duration of sampling. The area under the tissue concentration vs. time curves after anti-PCP Fab administration were decreased substantially in the brain (23% of controls), fat (24%), heart (52%), lung (74%) and testis (12%), but increased in the liver (137%). Because of anti-PCP Fab renal elimination, kidney PCP concentrations were significantly increased at all time points after Fab treatment (P < .05), which resulted in an 18-fold increase in the PCP area under the curve. These studies show anti-PCP Fab can rapidly remove PCP from the brain and maintain it in a highly bound form for a significant time.
Valentine
J L
JL
Department of Pharmacology and Toxicology College of Medicine University of Arkansas for Medical Sciences, Little Rock, USA.
Owens
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects*; D007074:Immunoglobulin G / Q000187:drug effects*; D008297:Male; D010622:Phencyclidine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D010622:Phencyclidine