The interplay between pharmacogenetics, concomitant drugs and blood levels of amitriptyline and its main metabolites.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Personalized medicine Pub Date : 2022-03-01 Epub Date: 2022-02-04 DOI:10.2217/pme-2021-0022

Luana Mifsud Buhagiar, Marilyn Casha, Anton Grech, Anthony Serracino Inglott, Godfrey LaFerla

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引用次数: 3

Abstract

Background: The research considers the impact of genotype-inferred variability on blood levels of amitriptyline and its main metabolites, as may be moderated by phenocopying. Patients & methods:CYP2D6 and CYP2C19 genotypes, and serum concentrations of amitriptyline, nortriptyline and hydroxymetabolites, were determined in 33 outpatients. Co-medications were reviewed to identify CYP inhibition risk. Results: CYP2C19 metabolizer status explained interpatient variation in nortriptyline to amitriptyline concentration ratios. The hydroxymetabolite to parent ratios increased with higher CYP2D6 activity scores and lower CYP2D6 inhibition risk. In patients at high CYP2D6 inhibition risk, the amitriptyline + nortriptyline concentration was, on average, 52% above the higher end of expected ranges. Conclusion: Practical construal of pharmacogenetics and drug interactions tantamount to aberrant metabolism can facilitate patient-tailored use of the established drug.

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药物遗传学、伴随药物与阿米替林及其主要代谢物血药水平之间的相互作用。

背景:该研究考虑了基因型推断的变异对阿米替林及其主要代谢物血液水平的影响，这可能通过表型复制来调节。患者与方法:测定33例门诊患者的CYP2D6、CYP2C19基因型及血清阿米替林、去甲替林、羟代谢物浓度。回顾联合用药以确定CYP抑制风险。结果:CYP2C19代谢状态解释了去甲替林与阿米替林浓度比的患者间差异。CYP2D6活性评分越高，CYP2D6抑制风险越低，羟基代谢物与亲本比值越高。在CYP2D6抑制风险高的患者中，阿米替林+去甲替林浓度平均比预期范围的上限高出52%。结论:对药物遗传学和药物相互作用等同于异常代谢的实际解释可以促进患者量身定制既定药物的使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Personalized medicine 医学-药学

CiteScore

3.30

自引率

4.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Personalized Medicine (ISSN 1741-0541) translates recent genomic, genetic and proteomic advances into the clinical context. The journal provides an integrated forum for all players involved - academic and clinical researchers, pharmaceutical companies, regulatory authorities, healthcare management organizations, patient organizations and others in the healthcare community. Personalized Medicine assists these parties to shape thefuture of medicine by providing a platform for expert commentary and analysis. The journal addresses scientific, commercial and policy issues in the field of precision medicine and includes news and views, current awareness regarding new biomarkers, concise commentary and analysis, reports from the conference circuit and full review articles.