| Stereochemistry | ABSOLUTE |
| Molecular Formula | C9H13N3O3 |
| Molecular Weight | 211.2178 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(=O)N(C=C1)[C@H]2CC[C@@H](CO)O2
InChI
InChIKey=WREGKURFCTUGRC-POYBYMJQSA-N
InChI=1S/C9H13N3O3/c10-7-3-4-12(9(14)11-7)8-2-1-6(5-13)15-8/h3-4,6,8,13H,1-2,5H2,(H2,10,11,14)/t6-,8+/m0/s1
The nucleoside analog 2',3'-dideoxycytidine (ddCyd), also known as Zalcitabine is a nucleoside analog reverse transcriptase inhibitor (NRTI) sold under the trade name Hivid. HIVID is indicated in combination with antiretroviral agents for the treatment of HIV infection. It is used as part of a combination regimen with antiretroviral agents. But it was discontinued by Roche Pharmaceuticals on December 31, 2006 due to the availability of newer HIV medicines. Within cells, zalcitabine is converted to the active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. Dideoxycytidine 5'-triphosphate inhibits the activity of the HIV-reverse transcriptase both by competing for utilization of the natural substrate, deoxycytidine 5'-triphosphate (dCTP), and by its incorporation into viral DNA. The lack of a 3'- OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation and, therefore, the viral DNA growth is terminated. The active metabolite, ddCTP, is also an inhibitor of cellular DNA polymerasebeta and mitochondrial DNA polymerase-gamma and has been reported to be incorporated into the DNA of cells in culture.
CNS Activity
Originator
Approval Year
Cmax
AUC
T1/2
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as victim
Sourcing
Sample Use Guides
Patients should be advised that HIVID is recommended for use in combination with active antiretroviral therapy. Greater activity has been observed when new antiretroviral therapies are begun at the same time as HIVID. Concomitant therapy should be based on a patient’s prior drug exposure. The recommended regimen is one 0.750 mg tablet of HIVID orally every 8 hours (2.25 mg HIVID total daily dose) in combination with other antiretroviral agents. Please refer to the complete product information for each of the other antiretroviral agents for the recommended doses of these agents. Based on preliminary data, the recommended HIVID dosage reduction for patients with impaired renal function is: creatinine clearance 10 to 40 mL/min: 0.750 mg of HIVID every 12 hours; creatinine clearance <10 mL/min: 0.750 mg of HIVID every 24 hours.
Route of Administration:
Oral
2',3'-Dideoxycytidine (DDC) was evaluated for prophylactic antiviral activity in vitro using the feline leukemia virus (FeLV)-cat animal model. In vitro antiviral activity of DDC against FeLV was dependent upon the target cell used for infection. DDC (5 to 10 microM) inhibited FeLV infection of feline lymphoid cells by greater than 80%, while 6.07 to 12.13 uM DDC was required to similarly inhibit infection of feline fibroblasts. However, 43 to 384 uM DDC was needed to inhibit FeLV infection of primary bone marrow cells by greater than 80%. These in vitro results suggest that, although relatively low doses of DDC may be adequate to prevent infection of feline lymphoid cells, 8- to 80-times-higher doses may be necessary to block infection of bone marrow cells, a primary target cell type for FeLV infection. Results of in vitro studies suggest that feline bone marrow cells may remain partially susceptible to FeLV infection at tolerated doses, while other somatic target tissues (i.e., lymphoid or epithelial tissues) may be protected from infection.
ACTIVE MOIETY
