Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain; Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.
Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.
Biomed Pharmacother. 2021 Jan;133:111087. doi: 10.1016/j.biopha.2020.111087. Epub 2020 Dec 8.
Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype is not related to olanzapine response or side effects. Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors (e.g. DRD2, HTR2C), and enzymes (e.g. UGT, CYP and COMT), in a cohort of healthy volunteers. Polymorphisms in CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were related to olanzapine pharmacokinetic variability. The incidence of adverse reactions was related to several genes: palpitations to ABCB1 and SLC22A1, asthenia to ABCB1, somnolence to DRD2 and ABCB1, and dizziness to CYP2C9. However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.
奥氮平是一种广泛用于治疗精神分裂症的非典型抗精神病药物，它常引起严重的药物不良反应。目前，尚无将遗传药理学信息应用于奥氮平的临床指南。此外，荷兰药物基因组学工作组（DPWG）指出，CYP2D6 表型与奥氮平的反应或不良反应无关。因此，本候选基因研究的目的是在健康志愿者队列中研究 21 个基因中的 72 个多态性对奥氮平药代动力学和安全性的影响，包括转运蛋白（如 ABCB1、ABCC2、SLC22A1）、受体（如 DRD2、HTR2C）和酶（如 UGT、CYP 和 COMT）。CYP2C9、SLC22A1、ABCB1、ABCC2 和 APOC3 的多态性与奥氮平的药代动力学变异性有关。不良反应的发生率与几个基因有关：心动过速与 ABCB1 和 SLC22A1 有关，乏力与 ABCB1 有关，嗜睡与 DRD2 和 ABCB1 有关，头晕与 CYP2C9 有关。然而，需要在患者中进行进一步的研究来证实这些遗传多态性对奥氮平药代动力学和耐受性的影响。
