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一项针对现实生活中精神分裂症患者CYP1A2基因多态性的奥氮平血药浓度的6年回顾性研究。

A 6-year retrospective study of olanzapine plasma concentration inpatients with schizophrenia CYP1A2 polymorphisms in real-life settings.

作者信息

Zhang Yan, Sun Lisha, Su Yanli, Wang Hui

机构信息

Xi'an Mental Health Center, 710100, Xi'an, Shaanxi, PR China.

Xi'an Key Laboratory of Pharmacy (Mental Health), 710100, Xi'an, Shaanxi, PR China.

出版信息

Heliyon. 2024 Oct 18;10(20):e39367. doi: 10.1016/j.heliyon.2024.e39367. eCollection 2024 Oct 30.

Abstract

AIM

to investigate the potential influence of CYP1A2 polymorphisms on olanzapine plasma concentration of inpatients with schizophrenia in real-life settings.

METHODS

409 inpatients who received OLA for at least 2 weeks, from June 2016 to March 2022 were included in the retrospective investigation. Moreover, 503 samples of above inpatients receiving OLA was built to investigate the influence of the relevant OLA plasma concentration, polymorphisms CYP1A2 -163C/A on the inpatients outcome.

RESULTS

Scale score reduction rate (SSRR) in 1 mutated CYP1A2 -163C/A alleles (CA) was significantly higher than other CYP1A2 alleles (CC + AA) (P = 0.002). Inverse S-curve correlations relationship was between SSRR and plasma concentrations of OLA (r = 0.130, P < 0.005). When remove ineffective subjects (ineffective group), the results of all CYP1A2 -163C/A genotype showed perfect correlations relationship tendencies with SSRR (r = 1.000). The best concentrations of OLA corrected for daily dose (C/D) range and the best concentration range of OLA of all CYP1A2 -163C/A genotype was 3.18-3.53 ng/mL/mg and 17.42-57.33 ng/mL. The C/D range and concentration range of OLA were 2.722-4.221 ng/mL/mg and 13.61-84.42 ng/mL, which belong CYP1A2 -163C/A CA genotype subjects, was largest.

CONCLUSIONS

The best effective C/D range and concentration range of OLA respective were 3.18-3.53 ng/mL/mg and 17.42-57.33 ng/mL, which range values of CYP1A2 -163C/A CA genotype of inpatients with schizophrenia was largest.

摘要

目的

探讨CYP1A2基因多态性对现实生活中精神分裂症住院患者奥氮平血药浓度的潜在影响。

方法

纳入2016年6月至2022年3月期间接受奥氮平治疗至少2周的409例住院患者进行回顾性研究。此外,构建503例上述接受奥氮平治疗的住院患者样本,以研究相关奥氮平血药浓度、CYP1A2 -163C/A基因多态性对住院患者结局的影响。

结果

1个CYP1A2 -163C/A等位基因突变(CA)的量表评分降低率(SSRR)显著高于其他CYP1A2等位基因(CC + AA)(P = 0.002)。SSRR与奥氮平血药浓度呈反向S曲线相关关系(r = 0.130,P < 0.005)。剔除无效受试者(无效组)后,所有CYP1A2 -163C/A基因型结果与SSRR均呈现出完美的相关关系趋势(r = 1.000)。所有CYP1A2 -163C/A基因型奥氮平校正日剂量后的最佳血药浓度(C/D)范围和最佳血药浓度范围分别为3.18 - 3.53 ng/mL/mg和17.42 - 57.33 ng/mL。属于CYP1A2 -163C/A CA基因型受试者的奥氮平C/D范围和血药浓度范围分别为2.722 - 4.221 ng/mL/mg和13.61 - 84.42 ng/mL,为最大。

结论

奥氮平最佳有效C/D范围和血药浓度范围分别为3.18 - 3.53 ng/mL/mg和17.42 - 57.33 ng/mL,其中精神分裂症住院患者CYP1A2 -163C/A CA基因型的范围值最大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11532838/b2b9a37ee3a2/gr1.jpg

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