| Indication |
For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals. |
| Pharmacodynamics |
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. |
| Mechanism of action |
Zalcitabine is a nucleoside reverse transcriptase inhibitor (NRTI)
with activity against Human Immunodeficiency Virus Type 1 (HIV-1).
Within cells, zalcitabine is converted to its active metabolite,
dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of
cellular enzymes. ddCTP interferes with viral RNA-directed DNA
polymerase (reverse transcriptase) by competing for utilization of the
natural substrate deoxycytidine 5'-triphosphate (dCTP), as well as
incorpating into viral DNA. Due to it's lack of a 3'-OH group, the
formation of a 5' to 3' phosphodiester linkage that is necessary for DNA
chain elongation is inhibited, thus leading to the termination of viral
DNA growth. |
| Absorption |
Bioavailability is over 80% following oral administration. |
| Volume of distribution |
|
| Protein binding |
Less than 4% |
| Metabolism |
Hepatic |
| Route of 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. |
| Half life |
2 hours |
| Clearance |
- 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour]
|
| 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 1½ weeks of treatment subsequent
to the development of a rash and fever. |
