Molecule

Drug Groups

approved

Description

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)

Indication

For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain.

Pharmacology

Methadone is a synthetic opioid analgesic with multiple actions quantitatively similar to those at morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, Methadone is more active and more toxic than morphine. Methadone is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The Methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.

Toxicity

In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.

Affected Organisms

Biotransformation

Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine.

Absorption

Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%.

Half Life

24-36 hours

Protein Binding

In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%).

Elimination

The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion.
Unmetabolized methadone and its metabolites are excreted in urine to a variable degree.

Distribution

* 1.0 to 8.0 L/kg

Clearance

* 1.4 to 126 L/h

References

External Links