An Investigation of O-Demethyl Tramadol/Tramadol Ratio for Cytochrome P450 2D6 Phenotyping: The CYTRAM Study

Autor: Blandine De La Gastine, Soizic Percevault, Laurent Varin, Nicolas Richard, Fabienne Fobe, Benoît Plaud, Georges Daccache, Vincent Compere, Jean-Jacques Parienti, Antoine Coquerel, Magalie Loilier, Nathalie Bleyzac, Laurent Bourguignon, Sylvain Goutelle, Véronique Lelong-Boulouard
Přispěvatelé: Hospices Civils de Lyon (HCL), Hôpital Privé d'Antony, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Service d'Anesthésie - Réanimation Chirurgicale [CHU Caen], Service d'anesthésie-réanimation-CTB, Université Paris Cité & AP-HP, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Direction de la Recherche Clinique et de l'innovation, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pharmacologie [CHU Caen], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Service de Pharmacologie, HUE, Erika
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmaceutics; Volume 14; Issue 10; Pages: 2177
Pharmaceutics
Pharmaceutics, 2022, 14 (10), pp.2177. ⟨10.3390/pharmaceutics14102177⟩
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics14102177
Popis: International audience; Cytochrome P450 2D6 (CYP2D6) gene polymorphisms influence the exposure to tramadol (T) and its pharmacologically active metabolite, O-demethyl tramadol (O-dT). Tramadol has been considered as a candidate probe drug for CYP2D6 phenotyping. The objective of the CYTRAM study was to investigate the value of plasma O-dT/T ratio for CYP2D6 phenotyping. European adult patients who received IV tramadol after surgery were included. CYP2D6 genotyping was performed and subjects were classified as extensive (EM), intermediate (IM), poor (PM), or ultra-rapid (UM) CYP2D6 metabolizers. Plasma concentrations of tramadol and O-dT were determined at 24 h and 48 h. The relationship between O-dT/T ratio and CYP2D6 phenotype was examined in both a learning and a validation group. Genotype data were obtained in 301 patients, including 23 PM (8%), 117 IM (39%), 154 EM (51%), and 7 UM (2%). Tramadol trough concentrations at 24 h were available in 297 patients. Mean value of O-dT/T ratio was significantly lower in PM than in non-PM individuals (0.061 ± 0.031 versus 0.178 ± 0.09, p < 0.01). However, large overlap was observed in the distributions of O-dT/T ratio between groups. Statistical models based on O-dT/T ratio failed to identify CYP2D6 phenotype with acceptable sensitivity and specificity. Those results suggest that tramadol is not an adequate probe drug for CYP2D6 phenotyping.
Databáze: OpenAIRE
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