{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:41:15Z","timestamp":1765294875286},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10]]},"abstract":"\n Background:<\/jats:title>\n A considerable interindividual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6<\/jats:italic> variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Information of methadone serum concentration, dose, age, sex, and CYP2C9<\/jats:italic>, CYP2C19<\/jats:italic>, and CYP2D6<\/jats:italic> genotypes were collected from a routine therapeutic drug monitoring database, whereas variant alleles in CYP2B6<\/jats:italic> and CYP3A5<\/jats:italic> were retrospectively genotyped. Linear mixed model analyses were used to study the impact of gene variants on methadone serum concentration\/dose (C\/D) ratios, including age, sex, and time since the last dose intake as covariates.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Overall, 155 serum samples from 62 patients were included in this study. The estimated mean methadone C\/D ratios was 17.8 nmol\u00b7L\u22121<\/jats:sup>\u00b7mg\u22121<\/jats:sup> for homozygous carriers of CYP2B6*6<\/jats:italic>, which was significantly (P<\/jats:italic> < 0.001) higher than noncarriers (9.2 nmol\u00b7L\u22121<\/jats:sup>\u00b7mg\u22121<\/jats:sup>). There was no difference in C\/D ratios between heterozygous carriers of CYP2B6*6<\/jats:italic> (9.1 nmol\u00b7L\u22121<\/jats:sup>\u00b7mg\u22121<\/jats:sup>) and noncarriers. An increase in mean methadone C\/D ratios was also seen for homozygous carriers of CYP3A5*3<\/jats:italic> and heterozygous carriers of CYP2C9*2<\/jats:italic> or *3<\/jats:italic> and CYP2C19*2<\/jats:italic> or *3<\/jats:italic>.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Patients homozygous for CYP2B6*6<\/jats:italic> had a >90% higher methadone C\/D ratio. Genotyping of CYP2B6<\/jats:italic> may therefore be of value when assessing dose requirements in methadone maintenance treatment.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000437","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T17:22:45Z","timestamp":1500398565000},"page":"550-555","source":"Crossref","is-referenced-by-count":33,"title":["Combined Effect of CYP2B6 Genotype and Other Candidate Genes on a Steady-State Serum Concentration of Methadone in Opioid Maintenance Treatment"],"prefix":"10.1097","volume":"39","author":[{"given":"Marianne K.","family":"Kringen","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Chalabianloo","sequence":"additional","affiliation":[{"name":"Department of Addiction Medicine, Haukeland University Hospital, Bergen;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Paul","family":"Bernard","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen G.","family":"Bramness","sequence":"additional","affiliation":[{"name":"Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Hamar;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Espen","family":"Molden","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo;"},{"name":"Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudrun","family":"H\u00f8iseth","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo;"},{"name":"Department of Forensic Sciences, Oslo University Hospital, Oslo; and"},{"name":"Norwegian Center for Addiction Research, University of Oslo, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230928","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3109\/15622975.2011.561872","article-title":"The world federation of societies of biological psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. 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