Page "Methadone" Paragraph 115

Methadone has a slow metabolism and very high fat solubility, making it longer lasting than morphine-based drugs.

Methadone has a typical elimination half-life of 15 to 60 hours with a mean of around 22.

However, metabolism rates vary greatly between individuals, up to a factor of 100, ranging from as few as 4 hours to as many as 130 hours, or even 190 hours.

This variability is apparently due to genetic variability in the production of the associated enzymes CYP3A4, CYP2B6 and CYP2D6.

Many substances can also induce, inhibit or compete with these enzymes further affecting ( sometimes dangerously ) methadone half-life.

A longer half-life frequently allows for administration only once a day in Opioid detoxification and maintenance programs.

Patients who metabolize methadone rapidly, on the other hand, may require twice daily dosing to obtain sufficient symptom alleviation while avoiding excessive peaks and troughs in their blood concentrations and associated effects.

This can also allow lower total doses in some such patients.

The analgesic activity is shorter than the pharmacological half-life ; dosing for pain control usually requires multiple doses per day.