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The Pharmacogenetics of Tramadol

  • Systematic Review
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Abstract

Background and Objective

Tramadol hydrochloride is used worldwide as an analgesic drug with a unique dual function. The metabolic enzymes cytochrome P450 (CYP) 3A4, CYP2B6, and CYP2D6 and the various transporters [adenosine triphosphate-binding cassette B1/multidrug resistance 1/P-glycoprotein, organic cation transporter 1, serotonin transporter (SERT), norepinephrine transporter (NET)] and receptor genes (opioid receptor μ 1 gene) give possible genetic differences that might affect the pharmacokinetics and/or pharmacodynamics of tramadol. Therefore, the aim of this review is to present a systematic walkthrough of all possible genetic factors involved in the pharmacology of tramadol.

Method

A systematic literature search was conducted in PubMed and EMBASE involving all metabolic enzymes, drug transporters and receptors, as well as SERT and NET that are involved in the pharmacokinetics and pharmacodynamics of tramadol. An additional search on population pharmacokinetics with genetic factors as covariates was performed separately.

Results

A total of 56 studies (45 cohort and case-control studies, three case reports, six in vitro studies, and two animal studies) were included.

Conclusion

In this systematic review, the current knowledge on all possible genetic factors that might influence the metabolism or clinical efficacy of tramadol has been collected and summarized. Only the effect of CYP2D6 polymorphisms on the metabolism of tramadol and the consequent effect on pain relief has been thoroughly studied and sufficiently established as clinically relevant.

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Acknowledgments

We thank the research librarian Johan Wallin for his support and advice in the literature research.

Conflict of interest

DL, PD and KB report no conflict of interest. No sources of funding were used in the preparation of this review.

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Authors and Affiliations

  1. Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark

    Dorte Lassen, Per Damkier & Kim Brøsen

  2. Department of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark

    Per Damkier & Kim Brøsen

  3. J.B. Winsloews Vej 19, 2nd floor, 5000, Odense, Denmark

    Dorte Lassen

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Lassen, D., Damkier, P. & Brøsen, K. The Pharmacogenetics of Tramadol. Clin Pharmacokinet 54, 825–836 (2015). https://doi.org/10.1007/s40262-015-0268-0

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