Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

• Main Authors: Victoria Rollason, Célia Lloret-Linares, Kuntheavy Ing Lorenzini, Youssef Daali, Marianne Gex-Fabry, Valérie Piguet, Marie Besson, Caroline Samer, Jules Desmeules
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Journal of Personalized Medicine
• Subjects: personalised medicine; cytochrome P450; P-glycoprotein; COMT; analgesic drugs; adverse drug reaction
• Online Access: https://www.mdpi.com/2075-4426/10/4/198

This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (<i>n</i> = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (<i>n</i> = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.