Comparative pharmacokinetics of new anti-HIV agents: 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine

A number of 2',3'-dideoxynucleosides have been shown to inhibit the in vitro infectivity and cytopathic effect of the human immunodeficiency virus (HIV). These compounds, as their 5'-triphosphates, inhibit viral reverse transcriptase by competing with the natural substrate at the same binding site on the enzyme. Dideoxynucleoside triphosphates can also be incorporated into growing DNA chains which then blocks further DNA elongation because they lack the 3'-hydroxyl group required for further polymerization. Among these nucleosides, 2', 3'-dideoxyadenosine 2',3'-dideoxyadenosine (ddA) and 2',3'-dideoxyinosine (ddI) show promising in vitro activity. Because adenosine is rapidly converted to inosine by adenosine deaminase, the in vivo conversion of ddA to ddI was studied to determine suitability of measuring plasma levels of ddI and to assess the bioavailability and pharmacokinetics of ddA. This report describes and compares the pharmacokinetics of ddA and ddI in the mouse.