Taylor D
Maudsley Hospital, London.
Br J Psychiatry. 1997 Aug;171:109-12. doi: 10.1192/bjp.171.2.109.
Metabolism of clozapine is complex and not fully understood. Pharmacokinetic interactions with other drugs have been described but, in some cases, their mechanism is unknown.
Published trials and case reports relevant to the human metabolism of clozapine and to suspected pharmacokinetic interactions were reviewed.
Metabolism of clozapine appears to be largely controlled by the function of the hepatic cytochrome p450IA2 (CYPIA2). Compounds which induce CYPIA2 activity (carbamazepine, tobacco smoke) may reduce plasma clozapine levels. Inhibitors of CYPIA2 (caffeine, erythromycin) have the opposite effect. Drugs which inhibit the hepatic cytochrome p4502D6 (CYP2D6) have also been reported to elevate plasma clozapine levels. The mechanism of this interaction is unclear.
The co-administration of clozapine and compounds reported to alter its metabolism should be avoided where possible. A host of other interactions can be predicted and so caution should be exercised when co-administering drugs which affect the function of CYPIA2 and CYP2D6. The pharmacokinetics of clozapine require further investigation so that its safe use can be assured.
氯氮平的代谢复杂，尚未完全明确。已报道了其与其他药物的药代动力学相互作用，但在某些情况下，其机制尚不清楚。
对已发表的与氯氮平人体代谢及疑似药代动力学相互作用相关的试验和病例报告进行了综述。
氯氮平的代谢似乎在很大程度上受肝细胞色素P450IA2（CYPIA2）功能的控制。诱导CYPIA2活性的化合物（卡马西平、烟草烟雾）可能会降低血浆氯氮平水平。CYPIA2抑制剂（咖啡因、红霉素）则有相反的作用。据报道，抑制肝细胞色素P4502D6（CYP2D6）的药物也会提高血浆氯氮平水平。这种相互作用的机制尚不清楚。
应尽可能避免氯氮平与据报道会改变其代谢的化合物合用。还可预测许多其他相互作用，因此在合用影响CYPIA2和CYP2D6功能的药物时应谨慎。氯氮平的药代动力学需要进一步研究，以确保其安全使用。
