Zalcitabine. Clinical pharmacokinetics and efficacy

• Published in: Clinical pharmacokinetics Vol. 28; no. 5; p. 351
• Main Authors: Devineni, D, Gallo, J M
• Format: Journal Article
• Language: English
• Published: Switzerland 01.05.1995
• Subjects: Animals; HIV Infections - drug therapy; Humans; Zalcitabine - pharmacokinetics; Zalcitabine - therapeutic use
• ISSN: 0312-5963
• DOI: 10.2165/00003088-199528050-00002

Zalcitabine (ddC) was the first drug to be approved under the US Food and Drug Administration's (FDA's) accelerated drug approval process. Zalcitabine is a potent nucleoside analogue inhibitor of reverse transcriptase used in the treatment of HIV infection. It is approximately 10-fold more potent than zidovudine (AZT) on a molar basis in vitro. Zalcitabine is well absorbed orally and reaches maximal plasma concentrations within 1 to 2 hours. In humans it is mainly eliminated by renal excretion of unchanged drug, and patients with renal failure may exhibit a prolonged half-life. A variety of clinical trials have evaluated the efficacy of zalcitabine based on improved survival and decreased frequency of opportunistic infections and on a surrogate marker of HIV disease, the CD4 count, or the concentration of an antigen associated with HIV, p24. Alternating zalcitabine therapy with zidovudine therapy was associated with increased CD4+ lymphocyte counts and reduced plasma p24 antigen levels. Zalcitabine can cause peripheral neuropathy (in 17 to 31% of patients), which is dose-related and is completely reversible when the drug is discontinued. Zalcitabine will continue to play a role in chemotherapeutic approaches to HIV.