The study medication was an experimental injectable sustained-release depot formulation of the medication buprenorphine. The injection is a suspension of biodegradable microcapsules each containing small amounts of the buprenorphine medication. As the microcapsules gradually disintegrate they provide a long-duration sustained release of buprenorphine. A tablet form of buprenorphine that is taken by holding it under the tongue is already used in the U.S. and around the world as an analgesic and as a treatment for opioid dependence; the tablet normally needs to be taken every day.
The recent study was the first to test this new long-lasting depot formulation in humans. The study examined the safety and pharmacokinetics of the depot medication, and tested its effectiveness for reducing the opioid withdrawal syndrome and for reducing the effects of opioid challenge injections.
Participants were five volunteer physically dependent heroin abusers. In a residential laboratory setting the heroin abusers each had their narcotics abruptly stopped and was instead given a depot injection of 58 mg of buprenorphine. For the next 6 weeks the patients were assessed repeatedly for signs and symptoms of the opioid withdrawal syndrome.
In addition, the volunteers received weekly challenge injections of the opioid hydromorphone (Dilaudid) to test whether their sensitivity to opioids was reduced by the depot buprenorphine treatment.
The results were promising both for prevention of the opioid withdrawal syndrome and for blockade of the opioid high from the hydromorphone challenge injections. No significant withdrawal syndrome occurred and no patient required additional medications. In addition, the effect of the opioid challenge injections appeared considerably reduced. No significant side effects were reported.
The ability of a single medication dose to have beneficial effects over 4 to 6 weeks is a significant finding for the treatment of opioid dependence. Further research will need to determine how this new product can best be used.
The depot medication holds promise both as a one shot detoxification treatment and as an alternative maintenance treatment. With the recent advent in the U.S. of office-based addiction treatment with sublingual buprenorphine, this longer-acting formulation could increase patient adherence to treatment, ease the visit burden on both patients and providers, and make treatment more accessible.
The study was conducted by researchers at the Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, under research grant support from the National Institute on Drug Abuse. The depot medication was developed and produced by Biotek, Inc. of Woburn, Massachusetts.
Authors were Bai-Fang X. Sobel, Stacey C. Sigmon, Rolley E. Johnson, Ira A. Liebson and George Bigelow from the Johns Hopkins University School of Medicine, and Elie S. Nuwayser and James H. Kerrigan from Biotek, Inc. The full text of the article is available online.