Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations

J Addict Dis. 2023 Jan-Mar;41(1):53-63. doi: 10.1080/10550887.2022.2057140. Epub 2022 Mar 31.


Background: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements.

Objectives: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations.

Methods: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis.

Results: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810).

Conclusions: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.

Keywords: BMI; CYP genotypes; Opioid agonist treatment; cirrhosis; liver fibrosis; methadone; serum concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Humans
  • Liver Cirrhosis / drug therapy
  • Methadone* / blood
  • Methadone* / therapeutic use
  • Opiate Substitution Treatment
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / genetics


  • Analgesics, Opioid
  • Methadone