An Explorative Study of CYP2D6's Polymorphism in a Sample of Chronic Pain Patients. Issue 5 (9th November 2019)

• Record Type: Journal Article
• Authors: Fanelli, Andrea; Palazzo, Chiara; Balzani, Eleonora; Iuvaro, Alessandra; Pelotti, Susi; Melotti, Rita Maria
• Is Part Of: Pain medicine. Volume 21:Issue 5(2020)
• Page Start: 1010
• Page End: 1017
• Publication Date: 2019-11-09
• Subjects: Chronic Pain -- CYP2D6 -- Phenocopying -- Drug–Drug Interaction -- Personalized Therapy; Pain -- Periodicals; Pain -- Treatment -- Periodicals; Analgesics -- Periodicals; Pain -- Periodicals; Pain Management -- Periodicals; Douleur -- Périodiques; Douleur -- Traitement -- Périodiques; Analgésiques -- Périodiques; Analgésique; Soulagement de la douleur; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.047205
• DOI: 10.1093/pm/pnz265
• Languages: English
• ISSNs: 1526-2375

Abstract

Abstract: Background: A proper antalgic treatment is based on the use of titrated drugs to provide adequate relief and a good tolerability profile. Therapies have a variable effectiveness among subjects depending on medical and genetic conditions. CYP2D6 variations determine a different clinical response to most analgesic drugs commonly used in daily clinical practice by influencing the drugs' pharmacokinetics. This study was a monocentric clinical trial exploring the CYP2D6 variants in 100 patients with a diagnosis of chronic pain. Methods: DNA was extracted to evaluate the genotype and to classify patients as normal-fast (gNMs-F), normal-slow (gNMs-S), ultrarapid (gUMs), intermediate (gIMs), and poor metabolizers (gPMs) using the Activity Score (AS). Information on therapies and general side effects experienced by patients was collected. Nongenetic co-factors were evaluated to examine the discrepancy between metabolic profile predicted from genotype (gPh) and metabolic profile (phenocopying). Results: The distribution of our data underlined the prevalence of the gNMs-F (67%), whereas gNMs-S were 24%, gIMs 6%, gPMs 3%, and no gUMs were found, resulting in 33% of patients with reduced metabolic activity. In the analyzed population sample, 86% and 56% of patients, respectively, took at least one or two drugs inhibiting in vitro activity of the CYP2D6 enzyme. Conclusions: Over one-third of the enrolled patients showed altered CYP2D6 enzymatic metabolic activity, with a risk of phenocopying potentially due to polypharmacology. Trial registration: ClinicalTrials.gov ID: NCT03411759.