triphosphate. Reverse transcriptase is the enzyme the virus uses to make a DNA copy of its RNA in order to insert its genetic material into the host's DNA. Upon incorporation into the DNA strand, stavudine triphosphate causes termination of DNA replication. Pharmacokinetics Absorption: Stavudine has rapid absorption and good oral bioavailability (F = 0.86). Distribution: Stavudine does not bind to proteins in the blood. Metabolism: The clearance of stavudine is affected minimally by hepatic metabolism. Oxidation and glucuronidation produce minor metabolites. Elimination: Stavudine is mostly eliminated in the urine and mostly in its unchanged form. Drug interactions Simultaneous use of zidovudine is not recommended, as it can inhibit the intracellular phosphorylation of stavudine. Other anti-HIV drugs do not possess this property. Stavudine is not protein-bound nor does it inhibit the major cytochrome P450 isoforms. Thus, significant drug interactions with drugs metabolized through these pathways or drugs that are protein-bound are unlikely. History Stavudine was first created by Jerome Horwitz in the 1960s and was originally named D4T. When the AIDS epidemic occurred in the 1980s, William Prusoff and Dr. Tai-Shun Lin discovered the anti-HIV properties of Stavudine. The pharmaceutical company Bristol-Myers Squibb manufactures the drug under the trade name Zerit. It is also the first drug to be granted parallel track status in 1992, by the US Food and Drug Administration (FDA), which allowed for the agency to make Stavudine available to patients before being approved. Stavudine was submitted under the FDA's accelerated approval process. Through this process, Stavudine's effectiveness was measured by its effect on the surrogate marker, CD4, instead of clinical endpoints. The FDA concluded that an increase in CD4 cell counts was an indicator of how effective the drug would be against AIDS and HIV infection. Stavudine was the fourth drug to be approved for the treatment of AIDS and HIV infection by the FDA on June 27, 1994. Even after approval, studies were continued to evaluate the clinical benefit of the drug. If there is no indication of clinical benefits, the accelerated approval may be withdrawn. In 2018, Mylan Pharmaceuticals discontinued manufacturing stavudine 20 mg, 30 mg, and 40 mg capsules. References External links Nucleoside analog reverse transcriptase inhibitors Bristol Myers Squibb Hepatotoxins Pyrimidinediones Wikipedia medicine articles ready to translate Dihydrofurans Withdrawn drugs Hydroxymethyl compounds