Overview of the Preclinical Development of an Antiretroviral Drug, 2′,3′-Dideoxyinosine

Treatment of Acute SIV infection in cynomolgus Monkeys with 2′,3′-dideoxyinosine (ddl) and 2′,3′-dideoxythymidiene (d4T)

“…Both ddl and d4T are supposed to inhibit HIV and SIV after phosphorylation by cellular enzymes to triphosphates (in case of ddl to ddA triphosphate) which then inhibit the reverse transcriptases of HIV and SIV (Ho and Hitchcock, 1989;Mansuri et el., 1989;McGowan et al, 1990). The phosphorylating enzymes in human and monkey cells are similar in their ability to phosphorylate nucleoside analogues (Habteyesus et el., 1991).…”

Antiretroviral therapy: reverse transcriptase inhibition

“…However, this study was limited by the common appearance at doses of greater than 0.09 mg/kg daily of a severe, painful peripheral neuropathy which appeared to be related to both the daily and the cumulative doses of ddC. It was also observed that at (49). ddA is also an effective antiretroviral agent in vitro, but in humans ddl as a prodrug of ddATP is preferable, because orally administered ddA is cleaved by acid in the stomach to form adenine and dideoxyribose, and the adenine product may cause nephrotoxicity.…”

“…ddA is also an effective antiretroviral agent in vitro, but in humans ddl as a prodrug of ddATP is preferable, because orally administered ddA is cleaved by acid in the stomach to form adenine and dideoxyribose, and the adenine product may cause nephrotoxicity. Like AZT, ddI may enter cells passively (49). ddl has been shown to be effective in vitro against HIV-1, HIV-2, human T-cell lymphotropic virus type 1, and simian immunodeficiency virus (49).…”

“…Like AZT, ddI may enter cells passively (49). ddl has been shown to be effective in vitro against HIV-1, HIV-2, human T-cell lymphotropic virus type 1, and simian immunodeficiency virus (49). ddI inhibits HIV infection in vitro at 1 to 10 ,uM, levels which are at least 10-to 20-fold lower than toxic levels (56).…”

The role of civil society in protecting public health over commercial interests: lessons from Thailand

“…February, 1998-US National Institutes of Health (NIH), 6 which invented didanosine, grants a licence to Bristol-Myers Squibb (BMS) to produce the drug in a limited list of countries, excluding Thailand, for an initial period of 10 years, with option of 5-year extension. Licence includes fair-pricing clause, stating that "there be a reasonable relationship between licensee's pricing of licensed product and the health and safety needs of the public and that this relationship be supported by evidence".…”