Clin Infect Dis. 1993 Feb;16 Suppl 1:S16-21. Unique Identifier :
The in vitro activity of didanosine (2',3'-dideoxyinosine, ddI) against
the human immunodeficiency virus (HIV) is generally less potent than
that of zidovudine (3'-azidothymidine, AZT) and zalcitabine
(2',3'-dideoxycytidine, ddC), often by an order of magnitude or more.
However, in monocyte/macrophage cell cultures, the potency of didanosine
is similar to, or greater than, that of zidovudine but still less than
that of ddC. The cytotoxicity of didanosine, including cytotoxicity to
bone marrow progenitor cells, is low, and endpoints are often not
reached. (The concentration inhibiting 50% of the cell growth [IC50] is
> 100 microM.) Thus, in spite of lower potency, didanosine has a high
antiviral selective index in vitro. By contrast, zidovudine and ddC are
more cytotoxic, with IC50 values < 5 microM. Clinically derived HIV
isolates with as high as 30-fold decreases in susceptibility to
didanosine in vitro have been described. However, in studies designed to
assess the frequency of resistance development after prolonged
didanosine therapy, more moderate changes (2- to 5-fold) are seen in
general. By contrast, isolates with a 100-fold decrease in sensitivity
to zidovudine are frequently found in strains from patients who have
received prolonged zidovudine therapy.
Comparative Study Didanosine/*PHARMACOLOGY/THERAPEUTIC USE
Dideoxynucleosides/*PHARMACOLOGY Human HIV/*DRUG EFFECTS Microbial
Sensitivity Tests JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL