Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications.

Autor: Chalabianloo F; Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Fadnes LT; Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Johansson KA; Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Høiseth G; Department of Forensic Medicine, Oslo University Hospital, Oslo, Norway.; Center for psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.; Norwegian Center for Addiction Research, University of Oslo, Oslo, Norway., Vold JH; Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway., Kringen MK; Center for psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway., Spigset O; Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Bramness JG; Institute of Clinical Medicine, UiT - Norway's Arctic University, Tromsø, Norway.; Department of Alcohol, Tobacco and Drugs, Norwegian Institute of Public Health, Oslo, Norway.; Norwegian National Competency Centre for Dual Disorder, Innland Hospital Trust, Hamar, Norway.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2024 Mar; Vol. 134 (3), pp. 333-344. Date of Electronic Publication: 2024 Jan 15.
DOI: 10.1111/bcpt.13975
Abstrakt: Background: A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood.
Objectives: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings.
Methods: 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.
Findings: A positive association was found between CDR and the homozygous CYP2B6*6 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.
Conclusions: 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.
(© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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