Didanosine

Didanosine (ddI) is a synthetic analog of deoxyadenosine. It is metabolized intracellularly by a series of cellular enzymes; its active moiety, 2,3-dideoxyadenosine-5-triphosphate, inhibits viral replication by competitive inhibition of HIV reverse transcriptase and by chain termination.

Pharmacokinetics: Absorption is decreased by food. Cerebrospinal fluid concentrations of the drug are approximately 20% of serum concentrations. The elimination half-life is 0.6-1.5 hours, but the intracellular half-life of the activated compound is approximately 12 hours. The drug is eliminated by glomerular filtration and tubular secretion.

Clinical Uses: Didanosine is effective in slowing clinical progression of disease in HIV-infected individuals when administered as monotherapy or in combination with zidovudine. The dosage should be reduced for low body weight.

Adverse Reactions: The major clinical toxicity associated with didanosine therapy is dose- dependent pancreatitis. Other reported adverse effects have included peripheral neuropathy, diarrhea, hepatotoxicity, hematocytopenias, and central nervous system toxicity (headache, irritability). A rise in uric acid during therapy with didanosine may precipitate attacks of gout in susceptible individuals.