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.