A review of the existing literature on buprenorphine pharmacogenomics

Patient Perceptions and Potential Utility of Pharmacogenetic Testing in Chronic Pain Management and Opioid Use Disorder in the Camden Opioid Research Initiative

“…Similarly unclear is whether variation in the CYP3A4 gene impacts buprenorphine response. One or two copies of the rs2740574 T allele (which has also been used to define the *1b haplotype) may increase the rate of buprenorphine metabolism and thereby increase the rate of withdrawal and decrease overall medication efficacy [21,22]. We did not find any significant differences or suggestive trends in baseline buprenorphine dosing in our modest cohort with respect to variation in either gene.…”

“…Published evidence for a potential PGx role in OUD medication management is less clear. Variation in the OPRM1 gene (rs1799971) potentially reduces the response to buprenorphine [20,21], and the G allele associated with potentially reduced response has also been implicated as a risk allele for opioid use disorder in genome-wide association studies [28]. Similarly unclear is whether variation in the CYP3A4 gene impacts buprenorphine response.…”

“…Buprenorphine is a partial, high-affinity mureceptor agonist shown to be an effective treatment for persons with opioid use disorder [19]. While there is some evidence that variation in the OPRM1 gene (rs1799971) potentially reduces the response to buprenorphine [20,21], and one or two copies of the CYP3A4 variant rs2740574 T allele (which has also been used to define the *1b haplotype) may increase the rate of buprenorphine metabolism and thereby increase the rate of withdrawal as well as decrease its overall efficacy [21,22], this evidence is not strong enough for CPIC to offer clinical guidelines for either drug-gene pair.…”

The history and pharmacology of buprenorphine: New advances in cats

“…Pharmacogenomic targets of buprenorphine associated with its PD and metabolic profile in humans include the genes coding for μ‐, δ‐, and κ‐opioid receptors, in addition to metabolism‐associated genes encoding cytochrome P450 enzymes and UGTs. The clinical implications for each polymorphism in humans have been reviewed (Meaden et al, 2021; Sadhasivam & Chidambaran, 2012).…”

Analysis of genetic and clinical factors associated with buprenorphine response

“…Genetic variation among patients can result in differences in medication effectiveness through pharmacokinetic and/or pharmacodynamic mechanisms. Despite growing support for a pharmacogenetic approach across a variety of medications [17], the literature on genetic moderators of OUD treatment effectiveness is limited [18]. Response to methadone among patients of European ancestry has been associated with single nucleotide variation in DRD2, ARRB2, ALDH5A1, MYOCD, and GRM6, as well as haplotypes in BDNF and OPRM1 [19][20][21][22][23][24].…”