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Subtherapeutic bupropion and hydroxybupropion serum concentrations in a patient with CYP2C19*1/*17 genotype suggesting a rapid metabolizer status

The Pharmacogenomics Journal volume 20, pages 840–844 (2020)Cite this article

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Abstract

Bupropion is hydroxylated to its primary active metabolite hydroxybupropion by cytochrome P450 enzyme CYP2B6. In vitro data suggest the existence of alternative hydroxylation pathways mediated by the highly polymorphic enzyme CYP2C19. However, the impact of its genetic variants on bupropion metabolism in vivo is still under investigation. We report the case of a 28-year-old male Caucasian outpatient suffering from major depressive disorder who did not respond to a treatment with bupropion. Therapeutic drug monitoring revealed very low serum concentrations of both bupropion and hydroxybupropion. Genotyping identified a heterozygous status for the gain-of-function allele with the genotype CYP2C19*1/*17 predicting enhanced enzymatic activity. The present case shows a reduced bupropion efficacy, which may be explained by a reduced active moiety of bupropion and its active metabolite hydroxybupropion, due to alternative hydroxylation pathways mediated by CYP2C19 in an individual with CYP2C19 rapid metabolizer status. The case report thus illustrates the clinical relevance of therapeutic drug monitoring in combination with pharmacogenetics diagnostics for a personalized treatment approach.

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Fig. 1: Serum concentration of bupropion and hydroxybupropion (in ng/mL) in relation to dose-related drug concentrations (DRC).

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Authors and Affiliations

  1. Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany

    Arnim Johannes Gaebler & Michael Paulzen

  2. JARA—Translational Brain Medicine, Aachen, Germany

    Arnim Johannes Gaebler & Michael Paulzen

  3. Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany

    Katharina Luise Schneider

  4. Centre for Translational Medicine, Medical Faculty of the University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Katharina Luise Schneider

  5. Institute of Clinical Pharmacology, Medical Faculty, RWTH Aachen, Wendlingweg 2, 52074, Aachen, Germany

    Julia Carolin Stingl

  6. Alexianer Hospital Aachen, Alexianergraben 33, 52062, Aachen, Germany

    Michael Paulzen

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  1. Arnim Johannes Gaebler
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  2. Katharina Luise Schneider
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Correspondence to Arnim Johannes Gaebler.

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MP has received speaker’s fees from the following pharmaceutical companies: Neuraxpharm, Lundbeck. He reports no conflict of interest with this publication. All other authors declare no conflict of interest.

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Gaebler, A.J., Schneider, K.L., Stingl, J.C. et al. Subtherapeutic bupropion and hydroxybupropion serum concentrations in a patient with CYP2C19*1/*17 genotype suggesting a rapid metabolizer status. Pharmacogenomics J 20, 840–844 (2020). https://doi.org/10.1038/s41397-020-0169-y

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  • DOI: https://doi.org/10.1038/s41397-020-0169-y

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