Didanosine

The second drug approved to treat HIV-1 infection was didanosine (dideoxyinosine, ddI), which is missing both the 2’- and 3’-hydroxyl groups. Upon entry into the host cell, ddI is biotransformed into dideoxyadenosine triphosphate (ddATP) through a series of reactions that involve phosphorylation of the ddI, amination to dideoxyadenosine monophosphate, and further phosphorylation. Like AZT, the resulting ddATP is incorporated into the DNA chain, causing termination of chain elongation. Due to its acid lability, absorption is best if ddI is taken in the fasting state. The drug penetrates into the CSF but to a lesser extent than does AZT. About 55 percent of the parent drug appears in the urine Pancreatitis, which may be fatal, is a major toxicity of ddI treatment and requires monitoring of serum amylase. The dose-limiting toxicity of ddI is peripheral neuropathy. Because of its similar adverse effect profile, concurrent use of stavudine is not recommended.diarrhoea hepatic dysfunction hyperurecemia cns effects alcoholic patients and those with hypertriglyceridemia reduced by food and chelating