Effect of isoprinosine on 3'-Azido-3'-deoxythymidine uptake and phosphorylation in human peripheral blood mononuclear cells.

The effect of the immunomodulating agent Isoprinosine on AZT uptake and phosphorylation in human blood monocytes/macrophages was examined. AZT (1-15 microM) uptake in monocytes/macrophages was rapid and dose- and time-dependent. The main metabolite formed after 1 h was AZT-5'-monophosphate. Isoprinosine cotreatment (5-50 microM) had no significant effect on AZT (5 microM) uptake. On the other hand, Isoprinosine increased the formation of AZT-diphosphate metabolites and, more intensively, of AZT-triphosphate (AZT-TP) metabolites after 1 h incubation. Extended exposure (4 h) resulted in complete absence of AZT-TP due to dephosphorylation of these metabolites or blocking of AZT phosphorylation.