WHY Methadone Liquid is DIFFERENT than Pill Methadone
Methadone hydrochloride in liquid form used for methadone maintenance patients compared to methadone tablets used to treat pain management patients is in fact
completely different. To clarify the difference, a vast amount of research has been done by examining the various patents of methadone hydrochloride, contacting the United States FDA, DEA, as well as various manufacturers of methadone hydrochloride in its various forms. Methadone HLC was originally synthesized by the Germans during World War II due to the lack of availability of opioid pain medications for those that required control of moderate to severe pain when morphine and other opioid analgesics where not available.
Methadone HLC is composed of two methadone isomers: d-methadone, and l-methadone. The final products in the USA contain both d-methadone, and l-methadone isomers leaving the final methadone products with various ratios of dl-methadone. Currently there are multiple different United States patents for making methadone HLC, at least six, as listed in the references below. It is currently completely baffling to the author as to why an FDA approved medication can be made with substantial varying effects and resulting in completely different molecular structures, yet named the same.
The amount of analgesia in any particular form of methadone is due to the ratio of DL-methadone dynamic factors. There seems to be increased potency presumably because of the NMDA receptor antagonism of the d-isomer. This is why the calculated equianalgesic dose of Methadone to Morphine can range from nearly 1:1 to as much as 12:1 in the USA. In other countries that use formulations of DL-methadone with nearly none of the D-Isomer included the equianalgesic ratio can be as high as 40+:1. Hypothetically with an empirically clean L-methadone mixture, eliminating the d-isomer and its NMDA receptor antagonism effects, the analgesia of Methadone to Morphine can be nearly 50:1 ratio.
Methadone has an asymmetric carbon atom resulting in 2 enantiomeric forms, (its purity) due to the D and L isomers. It is the racemic mixture of DL-methadone that is the form commonly used clinically in MMT settings. The D-Isomer of methadone also contains N-methyl-D-aspartate, the NMDA receptor antagonist activity; as such, this is the preferred substance to be dispensed in a clinical atmosphere to prevent opiate withdrawal as well as making it difficult for a person using the racemic mixture to feel the effects of any supplemental usage of opioid substances. This mixture of methadone is 90% D-methadone to 10% L-methadone and does not vary from various manufacturers.
L-methadone, with 50 times the analgesia potency of D-methadone, is used for somatic pain management. L-methadone is responsible for respiratory depression, QT interval prolongation as well as physical and psychological dependence. The United States does not allow for a patent that is 100% pure L-methadone, but limits the ratio of DL-methadone to a ratio of 60% L-methadone and 40% D-methadone with no NMDA receptor antagonism effects. As one can surmise from this combination of DL-methadone, it is the preferred method of delivery for those patients needing analgesia for moderate to severe discomfort. This is the Methadone HLC tablets dispensed by a pharmacy for pain, however even the non racemic forms of the pills seem to abide by their ‘patent of choice’, hence the Roxanne pills seem to be manufactured different than the Mallinckrodt version of their Methadose pill. After speaking directly with both mentioned manufactures as well as others, the claim that by use of the “Abbreviated New Drug Application”
(**), that it matters not what is used to make the various forms of Methadone, they all meet the FDA requirement that the end product is allowed to be dispensed as Methadone for USA consumption.
The author has a huge problem with this explanation; hence my continued effort to clarify the differences to clinicians in MMT and Pain management arenas.
It is the author’s intent to present this information clarifying the misunderstanding and belief that all methadone is the same.
(**): Link is included in the below references.
http://www.google.com/patents/US6897242
http://www.google.com/patents/US6008258
http://www.google.com/patents/US20100010096
http://www.google.com/patents/US3843696
http://www.google.im/patents/US5587381
http://www.fda.gov/Drugs/Developmen...ns/AbbreviatedNewDrugApplicationANDAGenerics/
http://www.ncbi.nlm.nih.gov/pubmed/9742275
http://en.wikipedia.org/wiki/Methadone
http://www.drugcite.com/label/...