Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications
Chalabianloo, Fatemeh; Fadnes, Lars T.; Johansson, Kjell Arne; Høiseth, Gudrun; Vold, Jørn Henrik; Kringen, Marianne K.; Spigset, Olav; Bramness, Jørgen Gustav
Peer reviewed, Journal article
Published version
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Date
2024Metadata
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- Institutt for klinisk og molekylær medisin [3619]
- Publikasjoner fra CRIStin - NTNU [39152]
- St. Olavs hospital [2620]
Original version
Basic & Clinical Pharmacology & Toxicology. 2024, 134 (3), 333-344. 10.1111/bcpt.13975Abstract
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.