title: Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Mamoonah
authors.initials: M
authors.lastname: Chaudhry
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Alessandrini
authors.affiliation: 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.
authors.forename: Jacobus
authors.initials: J
authors.lastname: Rademan
authors.affiliation: 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.
authors.forename: Tyren M
authors.initials: TM
authors.lastname: Dodgen
authors.affiliation: Department of Consumer Science, Faculty of Natural & Agricultural Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Francois E
authors.initials: FE
authors.lastname: Steffens
authors.affiliation: Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Danie G
authors.initials: DG
authors.lastname: van Zyl
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.affiliation: 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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
mesh_terms: D000639:Amitriptyline / Q000378:metabolism / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010865:Pilot Projects; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000639:Amitriptyline; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; activity score; adverse drug reactions; amitriptyline; diabetic neuropathy