Methadone conversion and pharmacology
Synthetic opioid with unique pharmacokinetics, used for complex chronic pain and opioid use disorder (OUD).
Equianalgesic estimate
Complex, dose-dependent conversion.
Published equianalgesic ratios vary between references and with clinical context. Read how to interpret conversion results before applying an estimate.
Mechanism of action
Racemic mixture. (R)-enantiomer: Mu-opioid receptor agonist. (S)-enantiomer: NMDA receptor antagonist and inhibitor of serotonin/norepinephrine reuptake.
Brand names: Dolophine, Methadose
Pharmacokinetics
- Protein binding
- ~85% (primarily alpha-1-acid glycoprotein)
- Volume of distribution
- 2-13 L/kg
- Half-life
- Extremely variable, typically 24-48 hours (Range 8-130+ hours).
| Route | Form | Bioavailability | Onset | Peak | Duration |
|---|---|---|---|---|---|
| Oral | — | 70-80% (Range 36-100%) | 30-60 min | 2.5-4 hours | 4-8 hours (Analgesia duration is significantly shorter than elimination half-life) |
Metabolism
- CYP3A4
- CYP2B6 (major)
- CYP2C19
- CYP2D6 (minor)
Metabolites
- EDDP Inactive.
Complex metabolism with high interindividual variability (esp. CYP2B6). Numerous CYP interactions (inhibitors increase risk of toxicity; inducers may cause withdrawal). Autoinduction may occur.
Renal and hepatic impairment
Renal
Considered safe in renal failure. Primarily fecal excretion of metabolites. Not removed by dialysis.
Hepatic
Use with caution; metabolism may be significantly impaired in severe liver disease (e.g., Child-Pugh C).
Clinical cautions
- Risk of QTc prolongation and Torsades de Pointes; ECG monitoring recommended.
- High risk of interaction with other QTc prolonging drugs and benzodiazepines.
- Risk of accumulation and delayed toxicity due to long, variable half-life.
- Equianalgesic conversion is complex and dose-dependent (ratio increases as prior opioid dose increases).
For qualified healthcare professionals. This page is an educational reference, not prescribing advice. Check medicine information and conversion factors against a current clinical source and local guidance.
Other opioids in this reference
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Last updated 30 August 2026. Read how to interpret conversion results and the Terms of Service.