Pohorecki R, Rayburn W, Coon W W, Domino E F
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Drug Metab Dispos. 1989 May-Jun;17(3):271-4.
Samples of human liver and placenta microsomes were analyzed for their in vitro hydroxylation capabilities using phencyclidine, [PCP, 1-(1-phenylcyclohexyl)piperidine] as substrate. Microsomes were prepared from full-term placentas (cesarean deliveries under epidural anesthesia) and from histologically normal liver specimens (staging laparotomies for Hodgkin's disease). Three different hydroxylated PCP metabolites were assayed including 1-(1-phenyl-3-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo-PCP), and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (4-OH-pip-PCP). The mean amounts of in vitro microsomal hydroxylation of PCP at the three different positions of the PCP ring varied considerably between individual samples of both liver and placenta. The placenta hydroxylated PCP but not as effectively as liver. Evidence for independent hydroxylation of PCP to 3-OH-cyclo-PCP was comparable to 4-OH-cyclo-PCP and 4-OH-pip-PCP. The formation of 3-OH-cyclo-PCP by the liver was enhanced in tobacco smokers. The formation of 4-OH-cyclo-PCP by the liver was negatively correlated with the stage of Hodgkin's disease even though the liver was free of disease in 11 of 12 subjects.
以苯环己哌啶[PCP，1-(1-苯基环己基)哌啶]为底物，分析人肝微粒体和胎盘微粒体的体外羟化能力。微粒体取自足月胎盘（硬膜外麻醉下剖宫产）和组织学正常的肝标本（霍奇金病分期剖腹术）。检测了三种不同的PCP羟化代谢产物，包括1-(1-苯基-3-羟基环己基)哌啶（3-OH-环-PCP）、1-(1-苯基-4-羟基环己基)哌啶（4-OH-环-PCP）和1-(1-苯基环己基)-4-羟基哌啶（4-OH-哌啶-PCP）。在PCP环的三个不同位置，PCP体外微粒体羟化的平均量在肝和胎盘的各个样本之间差异很大。胎盘可使PCP羟化，但效果不如肝脏。PCP独立羟化为3-OH-环-PCP的证据与4-OH-环-PCP和4-OH-哌啶-PCP相当。吸烟者肝脏中3-OH-环-PCP的形成增加。肝脏中4-OH-环-PCP的形成与霍奇金病的分期呈负相关，尽管12名受试者中有11名肝脏无疾病。
