2',3'-Dideoxyinosine (ddI) is in clinical trial as an anti-HIV agent. This unit is following the clinical pharmacology of this compound. Intravenously administered ddI has a half life of about 38 minutes. ddI is very acid labile; therefore for the phase I clinical trials the compound was given to fasting patients along with an oral antacid. The average oral bioavailability of this preparation was 38%. Other oral dosage forms were investigated to find a more convenient preparation and/or one with better bioavailability. CSF/plasma ratios and urinary excretion of ddI were measured also; CSF/plasma ratio averaged 21% for one point determinations, urinary recovery was 36%. It was determined that ddl had pharmacokinetic properties amenable to long term administration. Dextran sulfate (DS) has also been investigated as an anti-HIV agent and has generally been given orally. There is little reason to believe that this compound will be absorbed orally, however. To evaluate this, we administered tritium-labeled DS to rats. When administered intravenously, the compound had a plasma half-life of about 30 minutes, and partially degraded DS could be retrieved in the urine. No intact DS could be seen in either plasma or urine when the compound was administered orally. Thus it is unlikely that this compound will be useful as an oral medication.
