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

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Authors

Chaudhry, Mamoonah
Alessandrini, Marco
Rademan, Jacobus
Dodgen, Tyren Mark
Steffens, Francois E.
Van Zyl, Danie G.
Gaedigk, Andrea
Pepper, Michael Sean

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Publisher

Future Medicine

Abstract

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.

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Keywords

Activity score, Adverse drug reactions, Amitriptyline, CYP2D6, Diabetic neuropathy, Pharmacogenetics, Demethylation, Indomethacin, Management, Rats, Pain

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Citation

Chaudhry, M., Alessandrini, M., Rademan, J. et al. 2017, 'Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy : a pilot study ', Pharmacogenomics, vol. 18, no. 5, pp. 433-443.