Stavudine

Stavudine is an analog of thymidine, in which a double bond joins the 2’ and 3’ = carbons of the sugar. Stavudine is a strong inhibitor of cellular enzymes such as the β and γ DNA polymerases, thus reducing mitochondrial DNA synthesis and resulting in toxicity. The drug is almost completely absorbed on oral ingestion and is not affected by food. Stavudine penetrates the blood-brain barrier. About half of the parent drug can be accounted for in the urine. Renal impairment interferes with clearance. The major and most common clinical toxicity is peripheral neuropathy along with lipoatrophy and hyperlipidemia. Peripheral neuropathy is dose-limiting and increased with coadministration of didanosine or zalcitabine. Lactic acidosis with hepatic steatosis occurs more frequently with stavudine than with other NRTIs.