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

Autor:	Chaudhry M; 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., Alessandrini M; 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., Rademan J; 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., Dodgen TM; 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., Steffens FE; Department of Consumer Science, Faculty of Natural & Agricultural Sciences, University of Pretoria, Pretoria, South Africa., van Zyl DG; Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa., Gaedigk A; 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., Pepper MS; 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.
Jazyk:	angličtina
Zdroj:	Pharmacogenomics [Pharmacogenomics] 2017 Apr; Vol. 18 (5), pp. 433-443. Date of Electronic Publication: 2017 Mar 28.
DOI:	10.2217/pgs-2016-0185
Abstrakt:	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.
Databáze:	MEDLINE
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