DIDANOSINE
(Group 3)
VOL.: 76 (2000) (p. 153)
CAS No.:
Chem. Abstr. Name: 2¢,3¢-Dideoxyinosine
5.1 Exposure data
Didanosine is a nucleoside analogue which has been used since approximately 1990 in the treatment of HIV infection in adults and children. It is in widespread use in combination regimens with other antiretroviral agents, and potentiation of the antiviral effect of didanosine by hydroxyurea is being investigated.
5.2 Human carcinogenicity data
The only data available were from three trials designed to assess the efficacy of didanosine in improving the degree of immunocompetence and survival of patients with HIV infection, and no conclusion could be drawn about carcinogenicity.
5.3 Animal carcinogenicity data
No data were available to the Working Group.
5.4 Other relevant data
The human pharmacokinetics of orally administered didanosine is linear over a broad range of doses. Didanosine is about 40% bioavailable. It is rapidly absorbed, distributed and eliminated. About half of the human urinary metabolites are represented by hypoxanthine, and 40% is unchanged drug. Phosphorylation is a minor pathway but is essential for the antiviral activity of the drug.
The toxic effects of didanosine in humans include peripheral neuropathy, pancreatitis, hepatitis and leukopenia.
No relevant studies of the reproductive and prenatal effects of didanosine in humans were available. Didanosine crosses the placenta of women and monkeys by bidirectional, passive diffusion. Didanosine but not didanosine triphosphate was observed in placental and fetal tissues.
Little information was available on the genetic and related effects of didanosine. Didanosine was mutagenic in vitro and in vivo only at high doses. Treatment of human cells in culture significantly increased the mutant frequencies after short-term exposure to concentrations 10–20-fold greater than the peak plasma concentrations found in some patients. In the same studies, didanosine was more cytotoxic and less mutagenic than zidovudine.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of didanosine.
There is inadequate evidence in experimental animals for the carcinogenicity of didanosine.
Overall evaluation
Didanosine is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Synonyms
See Also:
Toxicological Abbreviations