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However, data from sub\u2010Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid\u2010addicted Tanzanian patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients attending MMT clinics (<jats:italic>n<\/jats:italic>\u2009=\u2009119) in Tanzania were genotyped for common functional variants of the <jats:italic>CYP3A4<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>CYP2A6<\/jats:italic>, <jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>ABCB1<\/jats:italic>, <jats:italic>UGT2B7<\/jats:italic> and <jats:italic>SLCO1B1<\/jats:italic> genotypes. Trough plasma concentrations of total methadone, S\u2010methadone (S\u2010MTD) and R\u2010methadone (R\u2010MTD), with their respective metabolites, 2\u2010ethylidene\u20101,5\u2010dimethyl\u20103,3\u2010diphenylpyrrolidine (EDDP), were quantified using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS). The methadone\u2010to\u2010EDDP metabolic ratio (MMR) was used to categorize the phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proportions of MMR\u2010predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. <jats:italic>CYP2B6<\/jats:italic> genotype significantly correlated with S\u2010methadone (<jats:italic>P<\/jats:italic>\u2009=\u2009.006), total methadone (<jats:italic>P<\/jats:italic>\u2009=\u2009.03), and dose\u2010normalized methadone plasma concentrations (<jats:italic>P<\/jats:italic>\u2009=\u2009.001). Metabolic ratios of R\u2010methadone (R\u2010MTD\/R\u2010EDDP), S\u2010methadone (S\u2010MTD\/S\u2010EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (<jats:italic>*6<\/jats:italic> or <jats:italic>*18<\/jats:italic>) than heterozygous or <jats:italic>CYP2B6*1\/*1<\/jats:italic> genotypes (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). The metabolic ratio for S\u2010MTD and total methadone was significantly higher among <jats:italic>ABCB1c.3435T\/T<\/jats:italic> than in the C\/C genotype. No significant effect of <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, <jats:italic>CYP3A4<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>CYP2A6<\/jats:italic>, <jats:italic>UGT2B7<\/jats:italic> and <jats:italic>SLCO1B1<\/jats:italic> genotypes on S\u2010methadone, R\u2010methadone, or total methadone was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Approximately one in six opioid\u2010addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the <jats:italic>CYP2B6<\/jats:italic> and <jats:italic>ABCB1<\/jats:italic> genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype\u2010based dosing algorithms for safe and effective therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16173","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T06:15:14Z","timestamp":1720764914000},"page":"2823-2836","source":"Crossref","is-referenced-by-count":5,"title":["<i>CYP2B6<\/i> and <i>ABCB1<\/i> genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania"],"prefix":"10.1111","volume":"90","author":[{"given":"Sabina","family":"Mugusi","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, School of Biomedical Sciences Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajabu 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