23dideoxyinosine

23dideoxyinosine, also known as didanosine or 2',3'-dideoxyinosine, is a purine nucleoside analog used as an antiretroviral agent in the treatment of HIV infection. It is the nucleoside form in which the ribose sugar lacks hydroxyl groups at the 2' and 3' positions, and it is phosphorylated by cellular kinases to the active triphosphate metabolite that inhibits HIV replication.

Mechanism of action: Didanosine triphosphate is a substrate for HIV reverse transcriptase and competes with natural deoxynucleotides. Incorporation into the viral DNA terminates chain elongation due to the absence of a 3'-hydroxyl group, thereby inhibiting viral DNA synthesis.

Medical use and administration: Didanosine has been used as part of combination antiretroviral therapy for HIV-1 infection. In many guidelines it is considered less favorable today because of toxicity concerns. It is administered orally and is best absorbed when taken on an empty stomach; food reduces bioavailability. Dosing often requires adjustment in renal impairment.

Pharmacokinetics: After oral administration, didanosine is absorbed and phosphorylated intracellularly to the active triphosphate, which inhibits viral replication. It is primarily eliminated by renal excretion, so renal function affects clearance.

Safety and adverse effects: Pancreatitis is a major and potentially serious toxicity associated with didanosine, and it can be fatal. Other significant adverse effects include peripheral neuropathy, lactic acidosis with hepatic steatosis, diarrhea, abdominal pain, and hepatic toxicity. Caution is advised in patients with a history of pancreatitis or liver disease; monitoring is recommended during therapy.

History and availability: Didanosine was approved in the 1990s under the brand Videx and widely used in early antiretroviral regimens. Due to toxicity concerns, its use has declined and it is less commonly prescribed in modern HIV treatment, though it remains available in some markets.