The goal of this program is to develop a bioerodible, controlled-release implant for the treatment of alcoholism. Specific Phase II aims are 1) to determine essential in vivo characteristics of a potent metabolite of disulfiram, 5-methyl N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO); 2) to develop candidate bioerodible implants to deliver that metabolite; and 3) to test the efficacy of those candidate implants in rats. The dose- response characteristics, toxicity, and basic pharmacokinetics of DETC- Meso will be determined to identify the target performance of the implants. A series of bioerodible beads will be prepared, and their controlled-release and biodegradation characteristics determined. Candidate beads will then be implanted into rats for in vivo determination of efficacy via inhibition of aldehyde dehydrogenase. The use of bioerodible implants should greatly improve patient compliance in alcoholism programs. The use of DETC-MeSO, which is much more potent than disulfiram, should enable reasonably small implants to be effective, and it is also expected to be a more effective drug than disulfiram. Substantial commercial interest in this technology for treatment of alcoholism is expected if the results of this program are successful, and the technology may also be useful for other types of drugs, such as narcotic antagonists and chemotherapeutic agents.
