Zalcitabine

Structural formula
General
Non-proprietary name	Zalcitabine
other names	4-Amino-1 - ((2 R , 5 S ) -5- (hydroxymethyl) tetrahydrofuran-2-yl) pyrimidin-2 (1 H ) -one ddC 2 ', 3'-dideoxycytidine Hivid
Molecular formula	C 9 H 13 N 3 O 3
External identifiers / databases
CAS number 7481-89-2 EC number 620-762-3 ECHA InfoCard 100.149.677 PubChem 24066 ChemSpider 22498 DrugBank DB00943 Wikidata Q2344582
Drug information
ATC code	J05 AF03
Drug class	Antiviral , nucleoside reverse transcriptase inhibitors
Mechanism of action	Competitive inhibition of reverse transcriptase
properties
Molar mass	211.218 g · mol -1
Physical state	firmly
Melting point	216-220 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 351 P: 281
Toxicological data	4,000 mg kg −1 ( LD 50 ,  mouse ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Zalcitabine (2 ′, 3′-dideoxycytidine, ddC ) is a chemical derivative of the nucleoside cytidine . Pharmacologically , it belongs to the nucleoside reverse transcriptase inhibitors (NRTIs), a group of antiretroviral substances. Zalcitabine is used to treat HIV- 1 infected patients as part of a combination antiretroviral therapy .

history

Zalcitabine was first produced in the 1960s by Jerome Horwitz as part of cancer research. The American cancer research center NCI then developed the substance as an HIV drug. It was the third antiretroviral agent to be approved by the FDA for the treatment of HIV and AIDS . In June 1992, zalcitabine was approved by the FDA as a monotherapy and in 1996 together with zidovudine (AZT) as a combination therapy . The substance was licensed by the NCI to Hoffmann-La Roche and marketed under the name Hivid until the end of 2006 . It has not been available in stores since December 31, 2006.

pharmacology

Zalcitabine is a pyrimidine derivative and an analogue of the natural deoxycytidine where the hydroxyl group in the 3-position of the tetrahydrofuran ring has been replaced by a hydrogen atom. The substance is converted into the active 5′-triphosphate, ddCTP, and then incorporated into the viral DNA. Because of the lack of a hydroxyl group, DNA synthesis is then terminated.

Pharmacokinetics

The mean oral bioavailability of zalcitabine is over 80%. Zalcitabine is only bound to plasma proteins to a very low extent (<4%). About 70% of an orally administered dose with a half-life of about two hours is excreted unchanged via the kidneys.

Drug interactions

Lamivudine (3TC) inhibits the intracellular phosphorylation of zalcitabine and therefore the two should not be taken together. It is also not recommended to take any additional substances that could cause polyneuropathy .

Side effects

Peripheral neuropathy is the most common . Fever , joint and muscle pain, and convulsions are less common .

Resistances

In comparison to zidovudine , HI viruses develop resistance to zalcitabine with difficulty, mainly in the HIV-pol gene. Cross resistance between zidovudine and zalcitabine has been observed.

Trivia

The substance also plays an important role in the Oscar- winning film Dallas Buyers Club from 2013. Under the name ddC , zalcitabine is one of the substances that the film hero illegally procures from Mexico in order to then sell it to people infected with HIV in Dallas because the FDA has not yet approved them.

Individual evidence

1. ↑ ^{a b c} data sheet 2 ′, 3′-Dideoxycytidine from AlfaAesar, accessed on March 16, 2014 ( PDF )(JavaScript required) .
2. ↑ United States Pharmacopoeia: Zalcitabine ( Memento April 7, 2014 in the Internet Archive ).
3. ^ FDA "Dear Health Care Professional" letter . June 2006 (English).
4. ↑ ^{a b} Zalcitabine Zeitschrift für Chemotherapie, Issue 3, 1994.
5. ↑ Lamivudine and Zalcitabine Drugs.com (English).
6. ↑ Zalcitabin Drugs.com (English).
7. ↑ ^{a b} Julie C. Adkins, David H. Peters, Diana Faulds: Zalcitabine. In: Drugs. 53, 1997, p. 1054, doi : 10.2165 / 00003495-199753060-00009 .
8. ↑ Dallas Buyers Club Internet Movie Database.

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