Phencyclidine pharmacokinetics and concentration-response relationships in the pigeon.
Phencyclidine (PCP) pharmacokinetics and drug discrimination were examined in pigeons (n = 6 in both groups) after intramuscular doses of 1.48 mg/kg. PCP absorption was rapid with maximum measured plasma concentrations ranging from 559 to 1450 ng/ml at 10-30 min after dosing, which corresponded to the time of maximum PCP stimulus effects in the drug discrimination studies. The terminal elimination half-life was 0.88 hr (harmonic mean). Average values for the volume of distribution and total body clearance were 1.6 l/kg and 18.2 ml/min/kg, respectively. In the behavioral studies, pigeons discriminated PCP-like effects from about 2 min to 2 hr after dosing. An average value for response on the PCP-appropriate key and for PCP concentration at each time point from 2 min to 2 hr was calculated from the individual subject data. Least-squares linear regression analysis of these data showed a highly significant relationship between the ability to discriminate PCP and log PCP concentration (y = 103x - 219, r2 = .810, p less than 0.005). This analysis suggests PCP concentration is a good predictor of behavioral efficacy.
Owens
S M
SM
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
McMillan
D E
DE
Hardwick
W C
WC
Wessinger
W D
WD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D010856:Columbidae / Q000378:metabolism* / Q000502:physiology; D004192:Discrimination, Psychological; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D008297:Male; D010622:Phencyclidine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D010622:Phencyclidine