Drug Groups

approved; investigational

Description

A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [PubChem]

Indication

For the treatment of human immunovirus (HIV) infections.

Pharmacology

Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

Toxicity

Side effects include peripheral neuropathy tingling, burning, numbness, or pain in the hands or feet), fatal lactic acidosis has been reported in patients treated with stavudine (ZERIT) in combination with other antiretroviral agents, severe liver enlargement, inflammation (pain and swelling) of the liver, and liver failure.

Affected Organisms

Biotransformation

Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase.

Absorption

Following oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).

Half Life

0.8-1.5 hours (in adults)

Protein Binding

Negligible

Distribution

* 46 ± 21 L

Clearance

* Renal cl=272 mL/min [Healthy subjects receiving 80 mg PO]
* 594 +/- 164 mL/min [HIV-infected adult and pediatric patients following 1-hour IV infusion]
* 9.75 +/- 3.76 mL/min/kg [HIV- Exposed or -Infected Pediatric Patients(Age 5 weeks – 15 years) following 1-hour IV infusion]

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