{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:50:05Z","timestamp":1791298205043,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T00:00:00Z","timestamp":1432252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid\u2010dependent responder patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighty\u2010one stable patients (60 men and 21 women, 43.7 \u00b1 8.1 years old, 63.1 \u00b1 50.9 mg day<jats:sup>\u22121<\/jats:sup> methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver\/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, <jats:italic>R<\/jats:italic>,<jats:italic>S<\/jats:italic>\u2010methadone trough concentration and clinically significant polymorphisms of the <jats:italic>OPRM1<\/jats:italic>, <jats:italic>DRD2<\/jats:italic>, <jats:italic>COMT<\/jats:italic>, <jats:italic>ABCB1<\/jats:italic>, <jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic> and <jats:italic>CYP2D6<\/jats:italic> genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Methadone maintenance dose was correlated to the highest dose ever used (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> = 0.57, <jats:italic>P<\/jats:italic> &lt; 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27\u201318.6, <jats:italic>P<\/jats:italic> = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01\u20132.44, <jats:italic>P<\/jats:italic> = 0.04), history of cocaine dependence (80 <jats:italic>vs<\/jats:italic>. 44 mg day<jats:sup>\u22121<\/jats:sup> in never\u2010addict patients, <jats:italic>P<\/jats:italic> = 0.005) and ethnicity (Asian &gt; Caucasian &gt; African, <jats:italic>P<\/jats:italic> = 0.04) were independently associated with high\u2010dose methadone in multiple regression analysis. A modest correlation was observed between liver\/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>] = 0.21, <jats:italic>P<\/jats:italic> = 0.06) but not with highest dose ever used (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub> = 0.15, <jats:italic>P<\/jats:italic> = 0.18) or dose\u2010normalized <jats:italic>R<\/jats:italic>,<jats:italic>S<\/jats:italic>\u2010methadone trough concentrations (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub> = \u22120.05, <jats:italic>P<\/jats:italic> = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and <jats:italic>R<\/jats:italic>,<jats:italic>S<\/jats:italic>\u2010methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver\/intestinal CYP3A4 activity in stable patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12576","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T07:46:14Z","timestamp":1419925574000},"page":"967-977","source":"Crossref","is-referenced-by-count":65,"title":["Methadone dose in heroin\u2010dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity"],"prefix":"10.1111","volume":"79","author":[{"given":"St\u00e9phane","family":"Mouly","sequence":"first","affiliation":[{"name":"Inserm  U1144 Paris F\u201075006 France"},{"name":"Universit\u00e9 Paris Descartes  UMR\u2010S1144 Paris F\u201075006 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