zalcitabine zalcitabine zalcitabine (2′-3′-dideoxycytidine, ddc), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (nrti) sold under the trade name hivid. zalcitabine was the third antiretroviral to be approved by the food and drug administration (fda) for the treatment of hiv/aids. it is used as part of a combination regimen. zalcitabineclinical datatrade nameshivid (discontinued)ahfs/drugs.commonographpregnancycategory au: d routes ofadministrationoralatc codej05af03 (who) legal statuslegal status uk: pom (prescription only) us: ℞-only in general: ℞ (prescription only) pharmacokinetic databioavailability>80%protein binding<4%metabolismhepaticelimination half-life2 hoursexcretionrenal (circa 80%)identifiers iupac name 4-amino-1-((2r,5s)-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1h)-one cas number7481-89-2 ypubchem cid24066iuphar/bps4828drugbankdb00943 ychemspider22498 yunii6l3xt8cb3ikeggd00412 ychebichebi:10101 ychemblchembl853 yniaid chemdb000006comptox dashboard (epa)dtxsid0023747 echa infocard100.149.677 chemical and physical dataformulac9h13n3o3molar mass211.221 g·mol−13d model (jsmol)interactive image smiles o=c1/n=c(/n)\c=c/n12o(cc2)co inchi 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 ykey:wregkurfctugrc-poybymjqsa-n y (verify) zalcitabine appears less potent than some other nucleoside rtis, has an inconvenient three-times daily frequency and is associated with serious adverse events. for these reasons it is now rarely used to treat human immunodeficiency virus (hiv), and it has even been removed from pharmacies entirely in some countries. history zalcitabine was first synthesized in the 1960s by jerome horwitz and subsequently developed as an anti-hiv agent by samuel broder, hiroaki mitsuya, and robert yarchoan at the national cancer institute (nci). like didanosine, it was then licensed because the nci may not market or sell drugs. the national institutes of health (nih) thus licensed it to hoffmann-la roche. zalcitabine was the third antiretroviral to be approved by the food and drug administration (fda) for the treatment of hiv/aids. it was approved on june 19, 1992, as a monotherapy and again in 1996 for use in combination with zidovudine (azt). using combinations of nrtis was in practice prior to the second fda approval and the triple drug combinations with dual nrtis and a protease inhibitor (pi) were not far off by this time. the sale and distribution of zalcitabine has been discontinued since december 31, 2006. mechanism of action zalcitabine is an analog of pyrimidine. it is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3' with a hydrogen. it is phosphorylated in t cells and other hiv target cells into its active triphosphate form, ddctp. this active metabolite works as a substrate for hiv reverse transcriptase, and also by incorporation into the viral dna, hence terminating the chain elongation due to the missing hydroxyl group. since zalcitabine is a reverse transcriptase inhibitor it possesses activity only against retroviruses. pharmacokinetics zalcitabine has a very high oral absorption rate of over 80%. it is predominantly eliminated by the renal route, with a half-life of 2 hours. drug interactions lamivudine (3tc) significantly inhibits the intracellular phosphorylation of zalcitabine to the active form, and accordingly the drugs should not be administered together. additionally, zalcitabine should not be used with other drugs that can cause peripheral neuropathy, such as didanosine and stavudine. adverse events the most common adverse events at the beginning of treatment are nausea and headache. more serious adverse events are peripheral neuropathy, which can occur in up to 33% of patients with advanced disease, oral ulcers, oesophageal ulcers and, rarely, pancreatitis. resistance resistance to zalcitabine develops infrequently compared with other nrtis, and generally only occurs at a low level. the most common mutation observed in vivo is t69d, which does not appear to give rise to cross-resistance to other nrtis; mutations at positions 65, 74, 75, 184 and 215 in the pol gene are observed more rarely. specialty drugs in 1992 dideoxycytidine was listed as a specialty drug. sources "zalcitabine (chebi:10101)". www.ebi.ac.uk. retrieved 2021-01-18. horwitz jr, chua j, da rooge ma, noel m, klundt il (january 1966). 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