RT info:eu-repo/semantics/article
T1 Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post‐surgical pain
A1 Casajús, Ana
A1 Zubiaur, Pablo
A1 Alday, Enrique
A1 Soria‐Chacartegui, Paula
A1 Saiz‐Rodríguez, Miriam
A1 Gutierrez, Lara
A1 Aragonés, Catalina
A1 Campodónico, Diana
A1 Gómez‐Fernández, Antía
A1 Navares‐Gómez, Marcos
A1 Villapalos‐García, Gonzalo
A1 Mejía‐Abril, Gina
A1 Ochoa, Dolores
A1 Abad‐Santos, Francisco
K1 Farmacogenómica
K1 Pharmacogenomics
K1 Tramadol
AB Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized β coefficients = 0.386 and 0.346, R2 = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized β coefficient = 0.224, R2 = 0.178), to lower PACU admissiontime (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response.Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC?Nowadays, CYP2D6 is considered the only clinically relevant pharmacogenetic biomarker for tramadol prescription; however, polymorphism of other metabolizing enzymes may be clinically relevant.WHAT QUESTION DID THIS STUDY ADDRESS?In this work, CYP2B6 genotype-informed phenotype was related to the response and tolerability to tramadol in patients with acute post-surgical pain.WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?CYP2B6 phenotype may be more relevant than previously thought in relation to tramadol prescription; our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts.HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?CYP2D6 was the main predictor of tramadol M1 metabolite concentrations but had a modest impact on drug effectiveness and safety.
PB ASCPT
SN 1752-8054
YR 2024
FD 2024-01
LK https://hdl.handle.net/10259/11918
UL https://hdl.handle.net/10259/11918
LA eng
NO P.S.-C. is financed by Universidad Autónoma de Madrid (FPI-UAM, 2021). G.V.-G. is co-financed by Instituto de Salud Carlos III (ISCIII) and the European Social Fund “Investing in Your Future” (PFIS predoctoral grant, number FI20/00090). M.N.-G. is financed by the ICI20/00131 grant, Acción Estratégica en Salud 2017–2020, ISCIII. P.Z. is financed by Universidad Autónoma de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. M.S.-R. contract was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, through the Sara Borrell Program (CD21/00022).
DS Repositorio Institucional de la Universidad de Burgos
RD 17-jul-2026