| Item |
Information |
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Drug Groups
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approved |
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Description
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A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of 5' to 3' phosphodiester linkages, which are needed for the elongation of DNA chains, thus resulting in the termination of viral DNA growth. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [PubChem] |
| Indication |
For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals. |
| Pharmacology |
Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. |
| Toxicity |
Acute overdose: Inadvertent pediatric overdoses have occurred with doses up to 1.5 mg/kg zalcitabine. Chronic overdose: in an initial dose-finding study in which zalcitabine was administered at doses 25 times (0.25 mg/kg every 8 hours) the currently recommended dose, one patient discontinued zalcitabine after 1? weeks of treatment subsequent to the development of a rash and fever. |
| Affected Organisms |
| • |
Human Immunodeficiency Virus |
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| Biotransformation |
Hepatic |
| Absorption |
Bioavailability is over 80% following oral administration. |
| Half Life |
2 hours |
| Protein Binding |
Less than 4% |
| Elimination |
Renal excretion of unchanged drug appears to be the primary route of elimination, accounting for approximately 80% of an intravenous dose and 60% of an orally administered dose within 24 hours after dosing (n=19). Renal clearance exceeds glomerular filtration rate suggesting renal tubular secretion contributes to the elimination of zalcitabine by the kidneys. |
| Distribution |
* 0.304 to 0.734 L/kg |
| Clearance |
* 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour] |
| References |
| • |
Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9.
[Pubmed]
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| • |
Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60.
[Pubmed]
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| External Links |
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