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.
Author: Dr Thileepan Naren MBBS FACRRM FRACGP
Thileepan is an Addiction Medicine Advanced Trainee and experienced general practitioner with a demonstrated history of working with disadvantaged and marginalized groups.