Pharmacokinetics and safety of a single dose of stavudine (d4T) in patients with severe hepatic impairment

Stavudine (2',3-didehydro-3'-deoxythymidine; also called d4T) is a thymidine nucleoside analog with potent in vitro activity against human immunodeficiency virus (HIV) type 1 at levels which are generally 100-fold below those that are cytotoxic. This open-label study enrolled five subjects with biopsy-proven cirrhosis and moderate to severe hepatic impairment (Child-Pugh classification grade B or C) and five age- and gender-matched controls. All subjects received a single 40-mg oral dose of stavudine (d4T). Stavudine pharmacokinetics in subjects with hepatic impairment were similar to those in age- and gender-matched control subjects and were not substantially different from those previously observed in human immunodeficiency virus-infected patients. Based on these findings, stavudine use does not require modification of the dose or dosing interval for patients with liver disease.