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Methadone serum concentrations and influencing factors: A naturalistic observational study.

Authors
  • Chalabianloo, Fatemeh1, 2
  • Westin, Andreas A3
  • Skogvoll, Eirik4, 5
  • Bramness, Jørgen G6, 7
  • Spigset, Olav3, 8
  • 1 Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway. [email protected] , (Norway)
  • 2 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. [email protected] , (Norway)
  • 3 Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. , (Norway)
  • 4 Clinic for Anaesthesiology and Intensive Care, St. Olav University Hospital, Trondheim, Norway. , (Norway)
  • 5 Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. , (Norway)
  • 6 Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Hamar, Norway. , (Norway)
  • 7 Institute of Clinical Medicine, UiT-Norway's Arctic University, Tromsø, Norway. , (Norway)
  • 8 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. , (Norway)
Type
Published Article
Journal
Psychopharmacology
Publication Date
Nov 01, 2019
Volume
236
Issue
11
Pages
3159–3167
Identifiers
DOI: 10.1007/s00213-019-05277-1
PMID: 31139877
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Although methadone maintenance treatment (MMT) has long been used for opioid addiction, our knowledge on its pharmacokinetics is still limited. We aimed to investigate effects of age, gender, and various co-medications on methadone serum concentration-to-dose ratio (CDR) in a naturalistic setting. In total, 4425 routine serum methadone concentrations obtained from 1691 MMT patients in the period October 1999 to July 2017 were included. Information about doses, age, gender, and concurrent medications was available in the laboratory database at the Department of Clinical Pharmacology at St. Olav University Hospital in Trondheim, Norway. A log-linear mixed model was used when analyzing the data. Mean age was 38.4 (range, 21-78) years and 70% were men. Mean CDR was 332 (range, 7-1776) (ng/mL)/(100 mg/d). Concomitant medication with at least one out of totally 170 drugs was recorded in 26% of the samples. CDRs were significantly lower in women (- 9%; confidence interval (CI), - 13%, - 4%; p = 0.001) and with concurrent use of CYP inducers (- 36%; CI, - 44%, - 28%; p < 0.001), but higher using CYP3A4 inhibitors as co-medications (+ 36%; CI, + 10%, + 68%; p = 0.005). Our results warrant taking into consideration gender differences in methadone metabolism as well as the impact of potential drug-drug interactions to obtain an optimal therapeutic effect and avoid adverse effects in MMT. Although the clinical implications of the altered drug levels require further study, our results call for close clinical monitoring of all patients undergoing MMT, preferably along with laboratory measurements of methadone serum concentrations.

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