Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients

Tanaka, Hiromu; Naito, Takafumi; Sato, Hajime; Hiraide, Takanori; Yamada, Yasuhide; Kawakami, Junichi

doi:10.1007/s00228-018-2527-0

Cited by 26 publications

(38 citation statements)

References 42 publications

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“…The nonresponse rate of tramadol treatment in patients with cancer pain was 27.8%, whereas 54.2% of cachectic patients with cachexia having cancer pain were nonresponders in our study. Tanaka et al 8 reported that the discontinuation rate of tramadol within 2 weeks in patients with cancer pain was 21%, which was consistent with our study.…”

Section: Discussionsupporting

confidence: 93%

“…The observational study reported that serum concentration of interleukin-6 (IL-6) was associated with the effect of tramadol. 8 Patients with cancer who discontinued tramadol treatment within 2 weeks had a higher serum concentration of IL-6 than those who completed the treatment for 2 weeks. 8 Most of the patients with a higher serum IL-6 concentration were reported to switch to strong opioids due to insufficient pain relief.…”

Section: Introductionmentioning

confidence: 92%

“…8 Patients with cancer who discontinued tramadol treatment within 2 weeks had a higher serum concentration of IL-6 than those who completed the treatment for 2 weeks. 8 Most of the patients with a higher serum IL-6 concentration were reported to switch to strong opioids due to insufficient pain relief. Cytokines produced by tumors and host tissues, including IL-6, were associated with cancer cachexia.…”

Section: Introductionmentioning

confidence: 92%

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Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study

Morio

Yamamoto

Yano

2020

Am J Hosp Palliat Care

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Objective: It was reported that the administration of tramadol in patients with cancer pain who have a higher interleukin 6 (IL-6) serum level led to insufficient pain relief. Cytokines produced by tumors, including IL-6, are associated with cancer cachexia. However, whether nonresponse to tramadol is related to cancer cachexia is unknown. The purpose of this study was to examine the relationship between tramadol response and cancer cachexia in patients with cancer pain. Methods: We conducted a retrospective cohort study of patients with cancer who received tramadol treatment for mild to moderate pain from January 2016 to June 2019. Patients who experienced <20% pain reduction based on the numeric rating scale from baseline to day 7 after treatment with tramadol were defined as nonresponders. Univariate and multivariate logistic regression analyses were conducted to examine the relationships between tramadol response and various patient characteristics, including cancer cachexia. Results: Of 115 patients, 79 were included in the analysis. A total of 24 patients experienced cancer cachexia, and 22 patients were nonresponders. In the univariate logistic analysis, cancer cachexia (odds ratio [OR]: 6.04, 95% confidence interval [CI]: 2.06-17.7), higher white blood cell counts (× 103/μL; OR: 1.28, 95% CI: 1.04-1.61), and lower body mass index (OR: 0.79, 95% CI: 0.66-0.96) were significantly associated with nonresponse to tramadol. The multivariate logistic analysis revealed that cancer cachexia (OR: 5.27, 95% CI: 1.75-15.9) was the only significant factor associated with nonresponse to tramadol. Conclusions: Cancer cachexia in patients with cancer pain can be associated with nonresponse to tramadol.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

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Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study

Morio

Yamamoto

Yano

2020

Am J Hosp Palliat Care

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“…With not much data available, the evidence of genetics on clinical outcomes is controversial. A recent study in cancer patients shows that CYP2D6 genotype impacts on plasma concentrations of tramadol and its demethylated metabolites, as well as drug tolerability [21]. On the other hand, previous data evidenced that although CYP2D6 genotypes had clear effects on the pharmacokinetics of opioids (namely oxycodone), no difference was found between the class of metabolizers in pain intensities, nausea, tiredness, and cognitive function [22].…”

Section: Cytochrome P-450 Genetic Variability and Opioid Pharmacokinementioning

confidence: 99%

“…CYP2D6 genotype impacts on plasma concentrations of tramadol and its demethylated metabolites, as well as drug tolerability [ 21 ].…”

Section: Figurementioning

confidence: 99%

Genetics and Opioids: Towards More Appropriate Prescription in Cancer Pain

Bugada

Lorini

Allegri

2020

Cancers

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Opioids are extensively used in patients with cancer pain; despite their efficacy, several patients can experience ineffective analgesia and/or side effects. Pharmacogenetics is a new approach to drug prescription based on the “personalized-medicine” concept, i.e., the ability of tailoring treatments to each individual’s genetic/genomic profile. Pharmacogenetics aims to identify specific genetic variants that influence pharmacokinetics and pharmacodynamics of drugs, better determining their effectiveness/safety profile. Opioid response is a complex scenario, but some gene variants have shown a correlation with pain sensitivity, as well as with opioid metabolism and clinical efficacy/adverse events. Although questions remain unanswered, some of these gene variants may already be used to identify specific patients’ phenotypes that are more prone to experience better clinical response (i.e., better analgesia and/or less adverse events). Once adopted, this approach to opioid prescription may improve a patient’s outcome. This review summarizes the available data on genetic variants and opioid response: we will focus on basic pharmacogenetic and its impact in the clinical scenario discussing how they may lead to more appropriate opioid prescription in cancer patients.

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The Role of Pharmacogenomics in Postoperative Pain Management

Sachtleben

Rooney

Haddad

et al. 2022

Methods in Molecular Biology

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Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients

Abstract: The 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.

Cited by 26 publications

References 42 publications

Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study

Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study

Genetics and Opioids: Towards More Appropriate Prescription in Cancer Pain

The Role of Pharmacogenomics in Postoperative Pain Management

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