ArticleEuropean journal of clinical pharmacology2018
Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.
Article in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study.International journal of molecular sciences · 2023Trial
- Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients.Cancer chemotherapy and pharmacology · 2023Article
- Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2023Review
- Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review.Journal of personalized medicine · 2022Review
- CYP2D6 pharmacogenetics and phenoconversion in personalized medicine.Expert opinion on drug metabolism & toxicology · 2022Review
- An Investigation of O-Demethyl Tramadol/Tramadol Ratio for Cytochrome P450 2D6 Phenotyping: The CYTRAM Study.Pharmaceutics · 2022Article
- Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits.Scientific reports · 2022Article
- Effects of UltramicronizedPharmaceutics · 2022Article
- Cancer cachexia: Pathophysiology and association with cancer-related pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- The Role of Pharmacogenomics in Postoperative Pain Management.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Different Pharmacokinetics of Tramadol,Frontiers in pharmacology · 2021Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeClinical responses to oral tramadol show a large variation in cancer patients. This study aimed to evaluate the impacts of cytochrome P450 (CYP) genotype and serum inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.
methodsThe predose plasma concentrations of tramadol and its demethylated metabolites were determined at day 4 or later in 70 Japanese cancer patients treated with oral tramadol. The CYP genotypes, serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the duration of tramadol treatment were evaluated.
resultsThe CYP2D6 genotype did not affect the plasma tramadol concentration. The plasma concentration of O-desmethyltramadol and its ratio to tramadol were lower in the CYP2D6 intermediate and poor metabolizer (IM + PM) group than in the normal metabolizer (NM) group (P = 0.002 and P = 0.023). The plasma concentration of N-desmethyltramadol and its ratio to tramadol were higher in the CYP2D6 IM + PM group than in the NM group (P = 0.001 and P = 0.001). The CYP2B6*6 and CYP3A5*3 alleles had no effect on the plasma concentrations of tramadol and its demethylated metabolites. The serum IL-6 and CRP levels were inversely correlated with the plasma concentration ratios of N-desmethyltramadol to tramadol and of N,O-didesmethyltramadol to O-desmethyltramadol. The serum IL-6 level was associated with the treatment duration of oral tramadol.
conclusionsThe CYP2D6 genotype but not the CYP2B6 and CYP3A5 genotypes affected the plasma concentrations of O- and N-desmethyltramadol through alteration of the tramadol metabolic pathway. The serum IL-6 level was associated with N-demethylation activity and tramadol tolerability.
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