Document Detail

MedLine Citation:
PMID:  8097417     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To review the chemistry, intracellular metabolism, pharmacokinetics, and clinical trials of zalcitabine (2'3'-dideoxycytidine, ddC). DATA SOURCES: English-language articles and conference procedings. The indexing terms used were zalcitabine, 2'3'-dideoxycytidine, and ddC. STUDY SELECTION: In addition to the manufacturer's package insert, available Phase I and Phase I/II studies were reviewed. DATA EXTRACTION: Clinical experience with ddC has been limited to uncontrolled studies and an expanded-access program. Efficacy was evaluated solely on surrogate markers of HIV disease: CD4+ lymphocyte counts and p24 antigen determinations. Clinical endpoints, such as disease progression and survival rates, must be provided to the Food and Drug Administration (FDA) for continued approval. DATA SYNTHESIS: The FDA has approved use of ddC in combination with zidovudine (ZDV) as therapy of HIV infection for patients with CD4+ lymphocyte counts < or = 300 cells/mm3 who have experienced significant clinical or immunologic deterioration. Although ddC has the same mechanism of action as other nucleoside analogs, it is more potent on a molar basis. The drug is stable in gastric pH and has good bioavailability (approximately 70-90 percent), but is rapidly cleared from plasma (half life approximately 1-3 h). Intracellular concentrations of ddC triphosphate, the active form, are probably related to plasma concentrations, yet may persist in cells longer than the parent drug persists in plasma. When used as primary therapy in patients with CD4+ < or = 300 cells/mm3, ddC/ZDV increased CD4+ lymphocyte counts and reduced plasma p24 antigen concentrations. In comparison to ZDV monotherapy data taken from other studies, ddC/ZDV appeared to demonstrate a more pronounced and sustained increase in CD4+ cell counts; however, this observation cannot be confirmed until the results of ZDV-controlled comparisons are available. Overall, 17-31 percent of the patients receiving the currently recommended initial dosage of ddC experience peripheral neuropathy. CONCLUSIONS: In combination with ZDV, ddC appears to augment the CD4+ cell response of ZDV monotherapy in the treatment of HIV infection for ZDV-naive patients, although controlled studies and rigorous statistical analyses are lacking at present. The efficacy of ddC/ZDV in patients who received prior treatment with ZDV monotherapy is unclear at the present.
M J Shelton; A M O'Donnell; G D Morse
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  The Annals of pharmacotherapy     Volume:  27     ISSN:  1060-0280     ISO Abbreviation:  Ann Pharmacother     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-05-21     Completed Date:  1993-05-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9203131     Medline TA:  Ann Pharmacother     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  480-9     Citation Subset:  IM; X    
American Foundation for AIDS Research, Center for Clinical Pharmacy Research, Buffalo, NY.
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MeSH Terms
CD4-Positive T-Lymphocytes / drug effects
Child, Preschool
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Drug Therapy, Combination
HIV Infections / drug therapy*
Zalcitabine / chemistry,  metabolism,  therapeutic use*
Zidovudine / therapeutic use
Reg. No./Substance:
30516-87-1/Zidovudine; 7481-89-2/Zalcitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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