Pharmacology
Methadone acts by binding to the µ-opioid receptor, but also has some affinity for the NMDA ionotropic glutamate receptor. Methadone is metabolized by CYP3A4, CYP2B6, CYP2D6 and is a substrate for the P-Glycoprotein efflux protein in intestine and brain. The bioavailability and elimination half-life of methadone is subject to substantial inter-individual variability. Its main route of administration is oral. Adverse effects include hypoventilation, constipation and miosis, in addition to tolerance, dependence and withdrawal difficulties. The withdrawal period can be much more prolonged than with other opiates, spanning anywhere from two weeks to several months. It can also be found in urine samples six to ten weeks after the last dose. It was generally thought it left the system 2–3 days after last use but this is not the case, many factors contribute to how long it will stay in the system. It depends an individual's body weight, metabolism, history of use/abuse and many more factors. In studies done on Methadone users going through detox, individuals experienced different withdrawal symptoms and withdrawal periods even though they received their last dose at the same time. When they gave blood and urine samples the methadone showed up in some individuals samples as much as four weeks after it was not evident in other individuals samples.
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