Methadone Absorption and Metabolism Variability

On Cracking Addiction this week

Methadone is a drug with a wide variability in its absorption with oral bio-availability ranges from 35% to 100%. This is a significant amount of variability and explains why the same dose of Methadone can impact different patients differently. Methadone is also highly protein bound and there is a four fold variability in Methadone's distribution within the body-further explaining the differing effects that can occur when taking Methadone.

Methadone is metabolised within the liver by the cytochrome P450 enzymes but mainly 3A4. There is a 17-fold inter-individual variation of methadone blood concentration for a given dosage and variations in metabolism account for a large part of this variation. Kinetic interactions influenced by the CYP 450 enzyme can affect plasma methadone levels.

• Inducers of CYP450 can
• Accelerate the metabolism of methadone
• lower methadone plasma levels
• Precipitate opioid withdrawal
• Inhibitors of CYP450 can
• Slow the metabolism of methadone
• Increase plasma levels
• Produce opioid toxicity (sedation, overdose)

Methadone is excreted renally with approximately 10% of drug renally eliminated unchanged. Renal excretion of methadone urinary pH dependent with increased Methadone excretion noted at pH less than 6 and decreased Methadone excretion at higher pH levels.