Impact of <i>ABCB1</i> and <i>CYP2B6</i> Genetic Polymorphisms on Methadone Metabolism, Dose and Treatment Response in Patients with Opioid Addiction: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse.</p><p>Objectives</p><p>To determine whether the <i>CYP2B6*6</i> or <i>ABCB1</i> (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).</p><p>Methods</p><p>Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the <i>CYP2B6*6</i> or <i>ABCB1</i> polymorphisms.</p><p>Results</p><p>We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in <i>CYP2B6*6</i> homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05–1.00, p = 0.03) with minimal heterogeneity (I² = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27–2.61, p = 0.02) however significant heterogeneity was observed (I² = 69%). Carriers of the <i>CYP2B6*6</i> haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the <i>ABCB1</i> polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.</p><p>Conclusion</p><p>Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the <i>CYP2B6*6</i> genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.</p></div