代谢
三种苯环己哌啶类似物——苯环己基二乙胺(PCDE)、苯环己基乙胺(PCE)和苯环己胺(PCA)在大鼠静脉给药后的药代动力学进行了测定。由于PCE和PCA是PCDE的主要代谢物，因此在给予PCDE后也测量了它们的血浆水平。同样，在给予PCE后也确定了PCA的浓度。数据被组合起来，并使用房室和非房室模型进行非线性回归分析，以确定PCDE代谢的动力学参数。目标是估计代谢序列PCDE到PCE到PCA的动力学常数。一个6室模型（每个分析物两个池）包括了对PCDE到PCE和PCE到PCA转化的可饱和部分，给出了与组合数据的最佳拟合。尽管某些微参数的不确定性很大，但在非饱和条件下，对于清除率、分布体积以及PCDE或PCE转化为PCE和PCA的分数，仍然获得了有用的估计。估计的PCDE转化为PCA的分数和PCDE转化为PCE的表观Km值与使用微粒体制剂在体外获得的值相当，这表明对于这类化合物的生物转化过程，体外代谢研究提供了合理的预测因子。
The pharmacokinetics of three phencyclidine analogs--phenylcyclohexyldiethylamine (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.
来源:Hazardous Substances Data Bank (HSDB)
