The Development of Sustained-Release Naltrexone and Clinical Use in Treating Opiate Dependence

Abstract

Heroin and related illicit opioid abuse continues to be a significant problem in the United States and globally, as measured by a variety of indicators. The ability of naltrexone to effectively antagonize heroin use is unequivocal. However, despite this pharmacological efficacy, noncompliance with oral naltrexone formu lae has been a significant impediment to its adoption as a treatment. Noncompliance is often associated with a patient' withdrawal from treatment and return to heroin use, although several recent studies specifically aimed at improving medication compliance have yielded promising results. An alternative method of naltrexone maintenance delivery involves the injection or surgical insertion of a sustained release preparation of naltrexone. This approach removes the onus on patients to use daily oral naltrexone. To date, a number of sustained release preparation of naltrexone have been developed for intramuscular or subcutaneous injection, or surgical insertion. Optimally, these products should be easy to administer, have no “major” adverse tissue reaction (biocompatible), be biodegradable, provide thera-peutically relevant blood naltrexone levels, and be clinically effective. This chapter reviews the history, development, and comments on the relative merits of different formulations.