Controlled Release Disulfiram (DS) Implant

Abstract

The inhibition of liver aldehyde dehydrogenase (ALDH) and subsequent increase in acetaldehyde after ethanol ingestion, form the basis for the clinical use of disulfiram (DS) in the treatment of alcoholism. This is referred to as the disulfiram-ethanol reaction (DER). A major problem associated with DS’s usefulness is patient compliance. DS implantation, however, could alleviate this concern. Unfortunately, the use of surgery required with implantation, and the apparent variability in producing a DER with implants, has limited the usefulness of this route of administration. Studies were therefore carried out to develop a cylindrical DS implant exhibiting high loading characteristics and a well-controlled range of release rates which could be implanted with a trochar. Specific objectives of these studies were to: 1) determine target doses from animal studies and to design prototype implants which meet these targets; 2) determine the in vivo release rates of DS from the prototype implants; 3) test the efficacy of prototype implants and correlate in vitro with in vivo release rates; and 4) determine the bioavailability of the implanted DS.