Didanosine
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Missing image Didanosine.png Chemical structure of didasonine. ddI | |
| 2'-3'-dideoxyinosine | |
| Molecular Weight | 236.23 |
| Empiric Formula | C10H12N4O3 |
| ATC code | J05AF02 |
| Metabolism | Renal elimination |
| Pregnancy category | C (USA) B2 (Aus) |
Didanosine (2'-3'-dideoxyinosine,ddI) differs from other nucleoside analogues, because it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Within the cell, ddI is, by cellular enzymes, phosphorylated to active metabolite of dideoxyadenosine triphosphate, ddATP. It acts as a chain terminator by incorporation and inhibits viral reverse transcriptase by competing with natural dATP.
Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid. Its oral absorption is fairly low (40 %) but rapid. The half-life in plasma is only 30 minutes, but in intracellular environment more than 12 hours. The kidneys actively secrete didanosine, the amount being 20 % of the oral dose. The side effects of didanosine are mainly headache and nausea, but also peripheral neuropathy, insomnia, pancreatitis and alterations of liver functions have been reported. Drug resistance to didanosine does develop, though slower than to AZT.
References
* Männistö P.T., Tuominen R.K. in Farmakologia ja Toksikologia, 5th edition: (ed. Koulu, Tuomisto, Paasonen) Medicina, 1996
* Rang H.P., Dale M.M., Ritter J.M.: Pharmacology, 3rd edition. Pearson Professional Ltd, 1995
* Watson et. al.: Molecular Biology of the Gene 4th edition. The Benjamin/Cummings Publishing Company, 1987