SBIR-STTR Award

Long-term objectives are to research treatment of intestinal diseases which complicate AIDS and HIV infection. This novel drug delivery capsule will be used to deliver high concentrations of antiviral drugs to the precise site of gastrointestinal infections in HIV infected patients. Using Zidovudine (ZDV) as the model compound, we will conduct a study in patients taking this drug. The study will have two specific aims: I) determine the precise site of ZDV absorption (stomach vs jejunum vs colon), and 2) Determine whether Gl absorption of ZDV is enhanced or compromised by AlDS-associated enteropathy. Patients taking ZDV will be recruited for a four-way randomized crossover pharmacokinetic study. Each will receive ZDV 100 mg on four occasions: IV (control), stomach release midjejunal release, and release at the ileocecal valve. ZDV and its metabolite (GZDV) will be assayed in collected bloods using RIA. Pharmacokinetic comparison will be made using AUC values after data fiting. Neither of the two specific aims have previously been addressed because there has not been a method capable of precise but non-invasive oral delivery to these Gl sites. These early site-specific absorption studies are a necessary prelude to treatment of infections at these sites.Awardee's statement of the potential commercial applications of the research: The eventual goal of these studies is the treatment of ileitis and/or colitis in patients with HIV infection, condition which currently must be treated with 10-21 days of IV medication. The site-specific oral delivery capsule allows oral delivery of antiviral medications to the site of colitis in high concentrations. This may lower the risks of side effects from systemic use of these same compounds.National Institute of Allergy and Infectious Diseases (NIAID)