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Updated: Oct 4, 2025

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
The interplay between pharmacogenetics, concomitant drugs and blood levels of amitriptyline and its main metabolites
Luana Mifsud Buhagiar1,2, Marilyn Casha3, Anton Grech4
1Department of Pharmacy, Faculty of Medicine & Surgery, University of Malta, Msida, MSD 2080, Malta.
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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