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.