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However, the underlying causes for this variability are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration\u2010to\u2010dose ratio (CDR) and discussed the clinical implications of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      A positive association was found between CDR and the homozygous\n                      <jats:italic>CYP2B6*6<\/jats:italic>\n                      genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcpt.13975","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:33:35Z","timestamp":1703118815000},"page":"333-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1242-1972","authenticated-orcid":false,"given":"Fatemeh","family":"Chalabianloo","sequence":"first","affiliation":[{"name":"Department of Addiction Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Global Public Health and Primary Care University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-2092","authenticated-orcid":false,"given":"Lars Thore","family":"Fadnes","sequence":"additional","affiliation":[{"name":"Department of Addiction Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Global Public Health and Primary Care University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-8710","authenticated-orcid":false,"given":"Kjell Arne","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Addiction Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Global Public Health and Primary Care University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-9536","authenticated-orcid":false,"given":"Gudrun","family":"H\u00f8iseth","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Oslo University Hospital  Oslo Norway"},{"name":"Center for psychopharmacology Diakonhjemmet Hospital  Oslo Norway"},{"name":"Norwegian Center for Addiction Research University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rn Henrik","family":"Vold","sequence":"additional","affiliation":[{"name":"Department of Addiction Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Global Public Health and Primary Care University of Bergen  Bergen Norway"},{"name":"Division of Psychiatry Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne 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