Department of Genetics, National Institute of Neurology & Neurosurgery, Manuel Velasco Suárez, La Fama, Tlalpan, Mexico City, 14269, Mexico.
Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, Orange, West Haven, CT 06477, USA.
Pharmacogenomics. 2022 Apr;23(6):371-392. doi: 10.2217/pgs-2022-0006. Epub 2022 Mar 21.
Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated with the concomitant use of alcohol. Additionally, pharmacogenetic studies have explored the influence of several genetic variants in CYP450, receptors and transporters involved in the interindividual response to CLZ. Herein, we systematically review the current multiomics knowledge behind the interaction between CLZ and alcohol intake, and how its concomitant use might modulate the pharmacogenetics. and other alleles not yet discovered could support a precision medicine approach for better therapeutic effects and fewer CLZ ADRs. CLZ monitoring systems should be amended and include alcohol intake to protect patients from severe CLZ ADRs.
氯氮平（CLZ）是一种用于治疗难治性精神病的非典型抗精神病药，但它与严重不良反应（ADR）的风险显著相关，而与酒精同时使用会加剧这种风险。此外，药物遗传学研究已经探讨了几个与 CYP450、受体和转运体相关的遗传变异对 CLZ 个体反应的影响。在此，我们系统地回顾了 CLZ 与酒精摄入相互作用的当前多组学知识，以及同时使用酒精如何调节药物遗传学。其他尚未发现的等位基因可能支持精准医疗方法，以获得更好的治疗效果和更少的 CLZ ADR。CLZ 监测系统应进行修正，包括酒精摄入，以保护患者免受严重的 CLZ ADR。
