Carrascal-Laso Lorena, Isidoro-García María, Ramos-Gallego Ignacio, Franco-Martín Manuel A
Servicio de Psiquiatría, Hospital Provincial de Zamora, IBSAL, 49071 Zamora, Spain.
Farmacogenética y Medicina de Precisión, Servicio de Bioquímica, Hospital Universitario de Salamanca, IBSAL, 37007 Salamanca, Spain.
J Clin Med. 2021 Sep 21;10(18):4275. doi: 10.3390/jcm10184275.
Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.
第二代抗精神病药物的代谢主要由具有高度多态性的细胞色素P450（CYP450）超家族完成。因此，了解不同已知CYP450多态性对抗精神病药物血浆水平的影响，进而了解其生物学效应，有助于更深入地认识个体间抗精神病药物治疗的变异性，并促使找到可能的解决办法。考虑到这一点，本综述旨在总结目前关于不同特征表型对最常用第二代抗精神病药物代谢影响的知识。四十项研究描述了与CYP1A2、CYP2D6、CYP3A4、CYP3A5和ABCB1基因相关的不同单核苷酸多态性（SNP）及其对奥氮平、氯氮平、阿立哌唑、利培酮和喹硫平药代动力学的影响。大多数作者得出结论，尽管不同表型之间的药代动力学参数可能存在显著差异，但仍需要更深入的研究来描述药代动力学相互作用和环境条件等其他变量，以全面理解这些药物遗传学相互作用。
