| Indication |
For the treatment of human immunovirus (HIV) infections. |
| Pharmacodynamics |
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. |
| Mechanism of action |
Stavudine inhibits the activity of HIV-1 reverse transcriptase
(RT) both by competing with the natural substrate dGTP and by its
incorporation into viral DNA. |
| Absorption |
Following oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%). |
| Volume of distribution |
|
| Protein binding |
Negligible |
| Metabolism |
Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase. |
| Route of elimination |
Not Available |
| Half life |
0.8-1.5 hours (in adults) |
| 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]
|
| 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. |
