A pharmacokinetic study of phenylcyclohexyldiethylamine. An analog of phencyclidine.
The pharmacokinetics of three phencyclidine analogs--phenylcyclohexyl-diethylamine (PCDE), phenylcyclohexylethylamine (PCE), and phenylcyclohexylamine (PCA)--were determined in rats after intravenous administration of each drug. Because PCE and PCA are major metabolites of PCDE, their plasma levels were also measured after administration of PCDE. Similarly, PCA concentrations was determined after administration of PCE. The data were combined and analyzed by nonlinear regression procedures using compartmental and noncompartmental models to determine the kinetic parameters of PCDE metabolism. The object was to estimate the kinetic constants for the metabolic sequence, PCDE to PCE to PCA. A 6-compartment model (two pools for each analyte) that included saturable components for the conversion of PCDE to PCE and PCE to PCA gave the best fit to the combined data. Despite large uncertainties for some microparameters, useful estimates were obtained for clearances, distribution volumes, and fraction of PCDE or PCE converted to PCE and PCA in vivo under nonsaturating conditions. The estimated fraction of PCDE converted to PCA and the apparent Km value for the conversion of PCDE to PCE were comparable to values obtained in vitro with microsomal preparations, suggesting that metabolic studies in vitro provide reasonable predictors of the biotransformation process in vivo for this class of compounds.
Cho
A K
AK
Department of Pharmacology, University of California, Los Angeles, School of Medicine 90024-1735.
Hiramatsu
M
M
Schmitz
D A
DA
Landaw
E M
EM
Chang
A S
AS
Ramamurthy
S
S
Jenden
D J
DJ
D000818:Animals; D001825:Body Fluid Compartments; D003514:Cyclohexylamines / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D010622:Phencyclidine / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D003514:Cyclohexylamines; C065947:phenylcyclohexyldiethylamine; C037320:1-phenylcyclohexylamine; D010622:Phencyclidine; C023851:N-ethyl-1-phenylcyclohexylamine