A review of the existing literature on buprenorphine pharmacogenomics

Abstract

Buprenorphine is an effective treatment for opioid dependence; however, it demonstrates individual variability in efficacy. Pharmacogenomics may explain this drug response variability and could allow for tailored therapy on an individual basis. The Food and Drug Administration and the Clinical Pharmacogenomics Implementation Consortium have guidelines on pharmacogenomic testing for some opioids (e.g., codeine); however, no guidelines exist for the partial opioid agonist buprenorphine. Pharmacogenomic testing targets for buprenorphine include pharmacodynamic genes like the mu-opioid receptor (MOP receptor) and catechol-O-methyltransferase (COMT), as well as the pharmacokinetic genes like the CYP enzymes. In this review we identified genotypes in patients with opioid addiction receiving buprenorphine that may result in altered therapeutic dosing and increased rate of relapse. The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D MOP receptor has been associated with variable efficacy and response to treatment in both adult and neonatal patients receiving buprenorphine for treatment of opioid withdrawal. An SNP associated with rs678849 of OPRD1, coding for the delta opioid receptor, was associated with opioid relapse as indicated by opioid positive urine drug screens; there was also sex specific SNP identified at rs581111 and rs529520 in the European American population. COMT variability, particularly in rs4680, has been associated with length of stay and need for opioid treatment in patients with neonatal abstinence syndrome. Variations of the pharmacokinetic gene for CYP3A4 showed that the ultrarapid metabolizer phenotype required higher doses of buprenorphine. Genotyping of patients may allow us to appropriately tailor buprenorphine therapy to individual patients and lead to improved patient outcomes; however, further research on the pharmacogenomics of buprenorphine is needed.

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The corresponding and last author, CDS, is responsible for the concept, content, design, and final editing of the article. The primary author, CWM, contributed much to the background research, content, and tables. The secondary and third author, AM and RA also contributed to much of the draft of the manuscript and assisted in the editorial process. All authors discussed the findings and implications and commented on the manuscript at all stages. All authors contributed extensively to the work presented in this paper.

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Correspondence to Cynthia D. Santos.

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Meaden, C.W., Mozeika, A., Asri, R. et al. A review of the existing literature on buprenorphine pharmacogenomics. Pharmacogenomics J (2020). https://doi.org/10.1038/s41397-020-00198-1

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