Methadone

Chemical

Orally active, synthetic opioid agonist

Use

  1. Opioid withdrawal
  2. Opioid substitution therapy
  3. Post op analgesia (20mg IV → 24hrs analgesia)

Presentation

Methadone = racemic

                         Dextro (+) → weak opioid agonist → NMDA antagonist

                         Levo (-) → an opioid

V high ionisation 99%

High lipid solubility co-eff 115

(PO) oral concentrate 10mg/mL

(IV) clear, colourless 10mg/mL

Dose

Titrated

  • Analgesic potency = 1 : 1 with morphine
  • But larger DoA >24hr only ¼ daily dosage of M needs to be given
  • Post op analgesia 20 mg IV → analgesia >24hr
  • When substituting for M, give a fixed dose 1/10 the total M dose up to a maximum of 30mg 

Route

PO (liquid for opioid use disorder) / Physeptone tablet / IV

Onset

Rapid depending on route of administration

  • Peak 1 – 2hrs IV/IM
  • Peaks 1 – 5hrs PO

DoA

>24hrs

10mg & variable t ½

MoA

µOP agonist

  • Comparable to M
  • Tolerance develops more slowly because it has higher efficacy due to effects on other receptor populations

NMDA antagonist

5HT3 uptake antagonism

α agonism

PD

PD

  • Analgesia
  • Less sedation & euphoria
  • Miosis – less prominent

PK

A

Good OBA

Variable up to 100%

Oral bioavailability approx. 65%

D

90% PPB → only a fraction enters CNS

M

Liver → inactive metabolites

CYP2D6 & 3A4 ; susceptible to induction/inhibition

E

Metabolites excreted in urine & bile

Elim t ½ prolonged

Variable 13 – 100hrs but on average 24hrs