ZALCITABINE - CLINICAL PHARMACOKINETICS AND EFFICACY

Zalcitabine (ddC) was the first drug to be approved under the US Food and Drug Administration's (FDA's) accelerated drug approval process, Z alcitabine is a potent nucleoside analogue inhibitor of reverse transc riptase used in the treatment of HIV infection. It is approximately 10 -fold more potent than zidovudine (AZT) on a molar basis in vitro. Zal citabine is well absorbed orally and reaches maximal plasma concentrat ions within 1 to 2 hours. In humans it is mainly eliminated by renal e xcretion of unchanged drug, and patients with renal failure may exhibi t a prolonged half-life, A variety of clinical trials have evaluated t he efficacy of zalcitabine based on improved survival and decreased fr equency of opportunistic infections and on a surrogate marker of HIV d isease, the CD4 count, or the concentration of an antigen associated w ith HIV, p24. Alternating zalcitabine therapy with zidovudine therapy was associated with increased CD4+ lymphocyte counts and reduced plasm a p24 antigen levels, Zalcitabine can cause peripheral neuropathy (in 17 to 31% of patients), which is dose-related and is completely revers ible when the drug is discontinued. Zalcitabine will continue to play a role in chemotherapeutic approaches to HIV.