While opiate agonists can be effective for treating abusers, they are. inappropriate in many circumstances. The opiate antagonist naltrexone (NTX) has been approved by the FDA and endorsed by NIDA and other government agencies as an important treatment alternative for heroin abuse. However, all authorities recognize that poor compliance greatly limits naltrexone's effectiveness. We propose to develop a novel, high-load, sustained release formulation of NTX that, by its nature, will improve compliance. As a 30-day, sustained release formulation, it should also enhance efficacy, patient acceptance and reduce side effects by eliminating the wide daily fluctuations in plasma levels and significant first pass metabolism associated with oral therapy. The specific aims of this proposal are to: (1) develop several novel formulations which can provide high sustained NTXplasma levels, while -avoiding the high bursts currently associated with high load formulations; (2) select a lead formulation based on initial in vivo pharmacokinetic testing; and (3) further evaluate the lead formulation for local irritability and pharmacokinetics. We will then proceed rapidly into clinical trials to demonstrate safety and efficacy of the formulation to achieve regulatory approval for treating opiate addicts
