Zalcitabine 2 3 -dideoxycytidine

Nevirapine = Viramune] (dipyridodiazepinone) [NRTIs in clinical use Abacavir (ABC) Adefovir dipivoxil (9-[2-Phosphonomethoxy)ethyl] -adenine PMEA) AZT Didanosine (= 2, 3 -Dideoxyinosine) Lamivudine Stavudine Zalcitabine (2, 3 -Dideoxycytidine]... 

WL Roberts, et al. Solid-phase extraction combined with radioimmunoassay for measurement of zalcitabine (2, 3 -dideoxycytidine) in plasma and serum. Clin Chem 40 211, 1994. 

Zalcitabine (2, 3 dideoxycytidine ddC) is a synthetic cytosine analog reverse-transcriptase inhibitor. It is active against HIV-I, HIV-2, and hepatitis B virus (HBV). The in vitro ICjo of zalcitabine against HIV-1 ranges from 2 nM in monocytes-macrophage cell lines to 0.5 pM in human peripheral blood mononuclear cells. Zalcitabine has considerably more antiretroviral activity in monocytes-macrophage cell lines than other nucleoside analogs, but the potential clinical utility of this observation is uncertain. 

Ci jHijBrjNO 4614-45-3) see Oxcarbazepine 3-acetyl-2,5-dichlorothiophene (CSH4CI2OS 36157-40-1) see Brinzolamide A -acetyl-2, 3 -didehydro-2, 3 -dideoxycytidine S -acetate (CJ3H15N3O5 62805-52-1) see Zalcitabine... 

At present there are seven NRTIs, which have been formally approved for the treatment of AIDS 3 -azido-2, 3 -dideoxythymidine (AZT, zidovudine), 2, 3 -dideoxyinosine (ddl, didanosine), 2, 3 -dideoxycytidine (ddC, zalcitabine), 2, 3 -didehydro-2, 3 -dideoxythymidine (d4T, stavudine), (—)-L-3 -thia-2, 3 -dideoxycytidine (3TC, lamivudine), cyclopentenyl V -cyclopropylaminopurine (abacavir, ABC), and (—)-L-5-fluoro-3 -thia-2, 3 -dideoxycytidine ((—)FTC, emtricitabine) (De Clercq 2004a) (Fig. 3). 

Pharmacology Zalcitabine, active against HIV, is a synthetic pyrimidine nucleoside analog of the naturally occurring nucleoside deoxycytidine in which the 3 -hydroxyl group is replaced by hydrogen. Within cells, zalcitabine is converted to the active metabolite, dideoxycytidine 5 -triphosphate (ddCTP), by cellular enzymes. ddCTP 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 DMA. 

The present NRTIs available for the treatment of HIV are zidovudine (azidothymidine, AZT), stavu-dine (d4T), didanosine (ddl), lamivudine (3TC), dideoxycytidine (ddC, zalcitabine) and abacavir, emtricitabine and tenofovir disoproxil. Combination formulations are abcavir combined with zidovudine and lamivudine and the abacavir-lamivudine combination. 

After oral administration, the bioavailability of zalcitabine is more than 80%. Food slightly interferes with its absorption. Sixty to eighty percent of the compound is excreted unchanged in the urine. Its (dideoxycytidine S -triphosphate) peak concentrations are at 2-3 h. The primary metabolite is dideoxyuridine, which is <15% of the administered dose. Zalcitabine is indicated in combination with other antiretroviral agents for the treatment of HIV infection. 

Therapeutic Function Antiviral, Immunosuppressive Chemical Name Cytidine, 2, 3 -dideoxy-Common Name Dideoxycytidine Zalcitabine Structural Formula ... 

Dideoxycytidine (DDC, zalcitabine), a nucleoside analogue that also inhibits reverse transcriptase, is more active than zidovudine in vitro, and (unlike zidovudine) does not suppress erythro-poiesis. DDC is not without toxicity, however, and a severe peripheral neurotoxicity, which is dose-related, has been reported. The chemical structures of DDC and of another analogue with similar properties, 2 3 -dideoxyinosine (DDI, didanosine), are presented in Fig. 10.25 (G, H, respectively). 

The oral bioavailability of zalcitabine is greater than 80%, and 60 to 80% of the parent compound is recovered unchanged in the urine. Food has a negligible effect on oral bioavailability. Clearance is greatly diminished in patients with compromised renal function, and daily doses should be reduced in this population. The half-life of intracellular dideoxycytidine 5 -triphosphate is estimated to be 2 to 3 hours. It is therefore recommended that zalcitabine be administered every 8 hours in patients with normal renal function. The CSF-plasma concentration ratio ranges from 0.09 to 0.37, although the clinical significance of CSF penetration is not known. 

Several 2, 3 -dideoxynucleosides are given to patients with HIV. These analogs include 3 -azido-2, 3 -dideoxythymidine (zidovudine, AZT), 2, 3 -dideoxycytidine (zalcitabine, ddC), 2, 3 -dideoxyinosine (didanosine, ddl), 2, 3 -didehydro-3 -deoxythymidine (stavudine, d4T), and (-)-2 -deoxy-3 -thiacytidine (lamivudine, 3TC). A related molecule is abacavir (ABC), which contains a cyclopentene-methanol moiety instead of the dideoxyribose moiety of the above-mentioned... 

Didanosine (DDi, 2, 3 -dideoxyinosine) and zalcitabine (DDC, 2, 3 -dideoxycytidine) are two other nucleoside analogs that are now used to treat... 

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