[Methadone--pharmacokinetics and pharmacodynamics of an opiate]

Methadone is described in this review as a potent analgesic agent; in Germany it is seldom administered as a therapeutic agent. It has the following pharmacokinetic properties: high lipophilicity, large volume of distribution (initial and steady state), low clearance (hepatic capacity limited) with a long terminal elimination time, high bioavailability following oral administration, and a tendency to accumulate in the blood and tissues. The review also considers pharmacodynamic aspects of methadone, which in Germany is available only in the levo-rotatory form; all the effects are conditioned by this l-enantiomer. In other countries methadone is successfully used over the following range of indications: intra- and postoperative pain (intravenous and epidural administration), cancer pain, and non-malignant painful conditions. The concepts of minimal effective analgesic concentration in the blood plasma (MEAC) and concentration required for 50% relief on pain are discussed. The MEAC is lower for the l-isomer than for the racemate. Methadone alone is a good analgesic agent that has slight effects in the form of respiratory depression, to which partial tolerance builds up in the course of long-term use of the drug. The interaction between methadone with alcohol, benzodiazepines, and barbiturates can be dangerous.