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Preliminary CommunicationOpen Accesscc iconby iconnc iconnd icon

Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study

    Mamoonah Chaudhry

    Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Marco Alessandrini

    Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Jacobus Rademan

    Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Tyren M Dodgen

    Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Francois E Steffens

    Department of Consumer Science, Faculty of Natural & Agricultural Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Danie G van Zyl

    Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    ,
    Andrea Gaedigk

    Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City & School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA

    &
    Michael S Pepper

    *Author for correspondence:

    E-mail Address: michael.pepper@up.ac.za

    Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Published Online:https://doi.org/10.2217/pgs-2016-0185

    Aim: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. Method: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced. Results: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity. Conclusion: Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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