The preclinical development of Medisorb Naltrexone, a once a month long acting injection, for the treatment of alcohol dependence.

摘要: Oral naltrexone, a nonselective opioid antagonist, is approved for the treatment of alcohol and dependence. However, efficacy oral naltrexone limited by poor patient compliance. To overcome this limitation, attempts have been made to develop an injectable extended-release formulation including encapsulation into biodegradable polymer microspheres (e.g. Medisorb Naltrexone, Vivitrex (naltrexone long acting injection)). In 1980, NIDA established development goals that they considered optimal formulation. At Alkermes, different formulations were tested with in vitro assays vivo models select lead Pharmacokinetic studies rats confirmed principle produced stable, pharmacologically relevant plasma levels approximately one month following single injection. The pharmacodynamic effects (antagonism morphine analgesia) corresponded well pharmacokinetic profile from same animals. While brain mu-opioid receptor density was found increase over time these rats, it did not appear affect ability suppress analgesia. Finally monkeys duration elevated concentrations naltrexone. Both PLG matrix which encapsulated are tolerated. Clinical trials currently ongoing dependent patients.