Luana Mifsud Buhagiar, Marilyn Casha, Anton Grech, Anthony Serracino Inglott, Godfrey LaFerla
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The interplay between pharmacogenetics, concomitant drugs and blood levels of amitriptyline and its main metabolites.
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.
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.
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