Methadone formulations

Myton T Fletcher K (2003). Descriptive study of the effects of altering formulation of prescribed methadone from injectable to oral. Psychiatric Bulletin, 27, 3-6... 

Steels MD, Hamilton M McLean PC (1992). The consequences of a change in formulation of methadone prescribed in a drug clinic. British Journal of Addiction, 87, 1549-54 Steinberg KL, Roffman RA, Carroll KM, Kabela E, Kadden R, Miller M Duresky D (2002). Tailoring cannabis dependence treatment for a diverse population. Addiction, 97, 135-42... 

Propoxyphene (Schedule II) is another opiate prescribed for pain which is much weaker than those mentioned above. Notice the structural similarities to methadone. Its effects last longer than many other drugs in this class which means it can be taken less frequently and the potential of abuse will be lessened. It can also be formulated with aspirin or acetaminophen in order to have a summation effect. 

Gum formulations containing caffeine showed rapid release and absorption of the agent with comparable bioavailability to the capsule form [57], Various gum formulations with vitamin C [56], diphenhydramine [58], methadone [59], and verapamil [60] have been developed and tested. 

Sample preparation procedures for GC are generially more involved. For example, for methadone hydrochloride, 0.5jV sodium hydroxide is added to give the free base, followed by extraction with methylene chloride. An internal standard is added after the extract is dried with anhydrous sodium sulfate [3, p. 970]. The assay of interleukin-la formulated with human serum albumin does not require any sample treatment prior to analysis by capillary electrophoresis [44]. 

SCHEDULE II Certain barbiturates, cocaine, codeine, codeine + acetaminophen (depends on dose and formulation), fentanyl (depends on dose), hydrocodone, hydromorphone, meperidine, methadone, morphine (depends on combination with other pain relievers), oxycodone, propoxyphene... 

Pierce et al. (1996) used slow release emulsion formulations of methadone to induce dependence in rats. Withdrawal was induced following i.p. challenge with either naloxone or saline, and dependence was assessed in terms of the presence or absence of characteristic withdrawal signs. 

Methadone is less likely to be diverted (traded on the black market) than shorter-acting drugs. In the UK a special Methadone Mixture 1 mg/ml (the concentration is part of the official title) is specially provided for the management of opioid addicts it is coloured green and formulated to prevent injection. ... 

Opioids are usually formulated as linctuses for antitussive use. Deciding on which agent to use depends largely on whether sedation and analgesia may be useful actions of the linctus. Hence methadone or diamorphine linctus may be preferred in patients with advanced bronchial carcinoma. In contrast, pholcodine, being nonsedating and nonaddictive, is widely incorporated into over-the-counter linctuses. 

In those who are opioid-dependent, methadone can facilitate adherence to HAART regimens. The pharmacokinetics of the tablet formulations of didanosine and stavudine have been studied in 17 individuals taking stable methadone therapy in comparison with 10 untreated controls (33). Methadone reduced the AUCo 6 by 63% for didanosine and by 25% for stavudine and the C ax by 66% and 44% respectively. These effects appeared to result primarily from reduced systemic availability. Trough concentrations of methadone were comparable to those seen in historical controls, suggesting that the nucleoside analogues did not affect methadone disposition. The authors concluded that larger doses of the tablet formulation (or another type of formulation) may be necessary to provide HAART in subjects taking methadone. 

Absorption Oral broavailability is variable depending On drug and formulation (morphine < hydrocodone and oxycodone < methadone). The exception is fentanyl, which is very poorly... 

Caution Resedation can occur when the naloxone wears off in 1-2 hours. Repeated doses of naloxone may be required to maintain reversal of the effects of opioids with prolonged elimination half-lives (eg, methadone) or sustained-release formulations or when packets or vials have been ingested. 

Zidovudine had no effect on methadone levels in one study, but there is one report of a patient requiring a modest increase in methadone dose after starting zidovudine. Similarly case reports describe patients requiring a modest increase in methadone dose after starting abacavir. Methadone can increase zidovudine serum levels, and reduce levels of abacavir, stavudine, and didano-sine from the tablet formulation, but not the enteric-coated capsule preparation. Tenofovir, and a single dose of zidovu-dine/lamivudine had no effect on methadone pharmacokinetics. 

The reduction in didanosine levels with methadone may be clinically relevant, and the authors suggest increasing the dose of the tablet formulation. Monitor virological response. The enteric-coated didanosine preparation is not affected and it may therefore be worth considering using this preparation instead. 

Friedland G, Rainey P, Jatlow P, Andrews L, Damle B, McCance-Katz E. Phannacokinetics of didanosine from encapsulated enteric coated bead formulation vs chewable tablet fonnu-lation in patients on chronic methadone dierapy. XIV International AIDS Conference, Barcelona, 2002. Abstract TuPeB4548. 

Methadone is a potent synthetic opioid analgesic, structurally unrelated to any of the opium-derived alkaloids. It is a highly lipophilic, basic drug (pKa 9.2) available as a hydrochloride powder formulation that can be reconstituted for oral, rectal, or parenteral administration. Methadone was developed in Germany in 1942 as a synthetic substitute for morphine, and has been approved and widely employed for opioid detoxification maintenance as well as acute and chronic pain management. 

Drug Formulations A novel tablet formulation of methadone was developed that exhibits decreased solubility in aqueous solutions while having unchanged bioavailability [54 ]. 

Vinson RK. Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Clin Drug Invest July 1,2012 32(7) 487-95. 

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