Stavudine

Biological Activity

Stavudine (d4T, brand name Zerit) is an orally bioavailable nucleoside analog reverse transcriptase inhibitor (NARTI) active against HIV. Stavudine triphosphate inhibits the HIV reverse transcriptase in vitro by competing with natural substrate, thymidine triphosphate. Stavudine also causes termination of DNA replication by incorporating into the DNA strand. In clinical studies, stavudine has excellent oral bioavailability in excess of 80%.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen.
Wangsomboonsiri W, et al. Clin Infect Dis. 2010 Feb 15;50(4):597-604. PMID: 20073992.

Antiretroviral activity of stavudine (2',3'-didehydro-3'-deoxythymidine, D4T).
Riddler SA, et al. Antiviral Res. 1995 Jun;27(3):189-203. PMID: 8540743.