Some factors affecting phencyclidine biotransformation by human liver and placenta

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.