Patients Given Zidovudine by Site-specific Oral Delivery

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: 1) determine the precise site of ZDV absorption (stomach vs jejunum vs colon), and 2) Determine whether GI absorption of ZDV is enhanced or compromised by AIDS-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, mid-jejunal 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 fitting. 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 GI sites. These early site-specific absorption studies are a necessary prelude to treatment of infections at these sites.