Holsztynska E J, Domino E F
Drug Metab Rev. 1985;16(3):285-320. doi: 10.3109/03602538508991437.
PCP is metabolized extensively in the body via a variety of metabolic routes. Biotransformation is a major mechanism of PCP elimination in humans and termination of PCP action in mice. In general, PCP metabolites are less active pharmacologically than PCP itself. Primary metabolism involves hydroxylation of the alicyclic rings at several carbon atoms by cytochrome P-450-mediated monooxygenase. Hydroxylation of the aromatic ring seems to be less likely and has not been conclusively demonstrated. Hydroxylation of PCP at carbon 2 of the piperidine ring to form the unstable carbinolamine leads to formation of a series of polar, open-ring compounds. Monohydroxylated metabolites are conjugated with glucuronic or sulfuric acid, or are further hydroxylated to dihydroxy derivatives that can also be subject to conjugation. Formation of highly reactive electrophilic metabolites of PCP have been demonstrated in vitro in microsomal preparations. Covalent modification of tissue macromolecules by reactive intermediates can be responsible for suicide inactivation of cytochrome P-450 and can possibly mediate some long-term toxic effects of PCP. PCP inhaled by cigarette smoking is metabolized via similar routes. About 50% of the PCP in cigarette smoke is converted to PC, a major product of thermal degradation of PCP. PC and its hydroxylated and conjugated metabolites appear to contribute little to the pharmacology or acute toxicity of PCP.
苯环己哌啶（PCP）在体内通过多种代谢途径被广泛代谢。生物转化是人类体内PCP消除以及小鼠体内PCP作用终止的主要机制。一般来说，PCP代谢产物的药理活性低于PCP本身。初级代谢包括细胞色素P - 450介导的单加氧酶使脂环在几个碳原子处发生羟基化。芳环的羟基化似乎不太可能，且尚未得到确凿证实。PCP在哌啶环的2位碳原子处羟基化形成不稳定的甲醇胺，导致一系列极性开环化合物的形成。单羟基化代谢产物与葡萄糖醛酸或硫酸结合，或进一步羟基化为二羟基衍生物，这些二羟基衍生物也可进行结合反应。在微粒体制剂中已在体外证实了PCP高活性亲电代谢产物的形成。反应性中间体对组织大分子的共价修饰可能是细胞色素P - 450自杀性失活的原因，并且可能介导PCP的一些长期毒性作用。通过吸烟吸入的PCP通过类似途径代谢。香烟烟雾中的PCP约50%转化为吡咯烷酮（PC），这是PCP热降解的主要产物。PC及其羟基化和结合代谢产物似乎对PCP的药理作用或急性毒性贡献不大。
