Inosine Pranobex and Zidovudine Metabolism

Antiviral drugs

“…It is suggested that combined therapy with inosiplex and zidovudine makes it possible to lower the dose of zidovudine and to prolong the dose interval. Moreover, inosiplex enhances the immunological response of the host [6]. Recently, it was described that treatment with inosiplex could delay progression to AIDS in a 24-week period in patients with HIV infection, but without manifest AIDS.…”

Effect of Isoprinosine on 3′-Azido-3′-Deoxythymidine Uptake and Phosphorylation in Human Peripheral Blood Mononuclear Cells

“…In conclusion: Isoprinosine increased AZT nucleotide formation through multiple mech anisms involving better plasma AZT avail ability [22] and increased intracellular phos phorylation of AZT.…”

“…Schinazi et al [10] showed that Isoprinosine was well tolerated at concentrations up to 640 \iM in cell culture, and did not enhance the HIV-1 yield when used alone or in combination with AZT in human peripheral blood cells. In clini cal studies, the administration of Isoprinosine with AZT in AIDS patients resulted in in creased half-life and plasma concentration of AZT [22], probably due to metabolic compe tition. It has been shown that intracellular phosphorylation of AZT and other dideoxynucleosides are major factors in their anti-HIV-1 effect [26].…”

“…It has been shown that intracellular phosphorylation of AZT and other dideoxynucleosides are major factors in their anti-HIV-1 effect [26]. In our study, the AZT con centrations were chosen for the following rea sons: (1) peak plasma concentrations of AZT varied from 1 to 2.5 gM in patients treated with the combination of AZT and Isoprino sine [22], and (2) 1 \iM AZT is sufficient to produce 93-100% viral suppression [27], Our results demonstrated that [3H]AZT accumu lation in human monocytes/macrophages was neither dose-nor time-dependent. This is in agreement with results reported for bone mar row cells [24], and the monocyte cell line [3], We also reported that the formation of AZT-MP was greater than the level of AZT-DP and AZT-TP.…”

“…It has been reported that Isoprinosine produced weak anti-HIV type 1 (HIV-1) activity in hu man peripheral blood mononuclear cells and H9 cells and restored in vitro the impaired T helper cells from AIDS patients [20,21], However, immunomodulators such as Isopri nosine are unlikely to be effective antiviral drugs. However, in clinical studies, the ad ministration of Isoprinosine in AIDS patients treated with AZT resulted in an increased half-life and plasma concentration of AZT [22], probably due to metabolic competition. In this study we examined whether this drug will enhance the pharmacological activity of AZT when used in combination with other agents.…”