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Methadone Absorption and Metabolism Variability

December 21, 20211 min read

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.

Methadone absorption variabilityMethadone metabolismCytochrome P450 enzymesMethadone distributionRenal excretion of methadonePharmacokinetic interactions
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Dr Thileepan Naren

Dr. Thileepan Naren, an esteemed medical professional, holds prestigious qualifications including MBBS, FACRRM, FRACGP, and FAChAM, showcasing his extensive expertise in the field. Renowned as an Addiction Medicine Specialist, he brings a wealth of experience to the forefront, particularly in catering to the needs of disadvantaged and marginalised communities. With a proven track record, Dr. Naren exemplifies dedication and compassion in providing comprehensive healthcare solutions to those in need.

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