Atazanavir

Structural formula
General
Non-proprietary name	Atazanavir
Molecular formula	C 38 H 52 N 6 O 7
External identifiers / databases
EC number	812-543-8
ECHA InfoCard	100.243.594
PubChem	148192
ChemSpider	130642
DrugBank	DB01072
Wikidata	Q423467
Drug information
ATC code	J05 AE08
Drug class	HIV protease inhibitors
properties
Molar mass	704.86 g · mol -1
Physical state	firmly
Melting point	207-209 ° C
solubility	almost insoluble in water
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Atazanavir (ATV, trade name Reyataz ^® ) is a drug that is used in oral dosage forms to treat HIV infections and belongs to the group of HIV protease inhibitors . The approval by the American FDA took place in June 2003, by the European Commission in March 2004. The license holder is the pharmaceutical company Bristol-Myers Squibb .

Indication and effectiveness

Atazanavir is approved for the treatment of HIV infection in adults. Compared to previous representatives of the same drug class must atazanavir advantageously be fed only once a day and may in the course of highly active antiretroviral therapy ( HAART ) with drugs from the group of transcriptase inhibitors ( NRTIs are combined).

The effectiveness was compared with other HIV protease inhibitors ( nelfinavir and lopinavir / ritonavir ) as well as with efavirenz and the clinical studies involved showed a similar potency.

Pharmacokinetics

With atazanavir, unlike other HIV protease inhibitors, a single dose per day is sufficient to achieve effective plasma levels. Simultaneous food intake has a positive effect on bioavailability , while simultaneous intake of certain drugs can reduce absorption . In the blood 86% of the active ingredient are in protein-bound front shape. It is metabolized mainly in the liver by cytochrome P450- dependent monooxygenases . The elimination is carried out with a mean plasma half-life of about 7 hours.

Mechanism of action

Atazanavir is a so-called HIV protease inhibitor and as such interferes with the reproductive mechanism of HI viruses. Atazanavir binds to the viral enzyme HIV protease , preventing it from working. Affected cells are no longer able to reproduce functioning viruses, and the viral load decreases.

Atazanavir is combined with a second HIV protease inhibitor, similar to lopinavir. This has the task of slowing down the breakdown of atazanavir in the liver and thus making the active ingredient available to the organism over a longer period of time.

Side effects and interactions

Overall, the tolerability of atazanavir compared to other representatives of the HIV protease inhibitors is assessed better. Disorders of the gastrointestinal tract , such as abdominal pain, nausea and diarrhea, as well as disorders of lipid metabolism ( hyperlipidemia and lipodystrophy ) and increased cholesterol levels are observed less frequently during therapy with atazanavir than with the above-mentioned comparison substances. However, increased bilirubin levels in the blood and, as a result, jaundice occasionally lead to discontinuation of therapy.

As with the other HIV protease inhibitors, atazanavir also poses the problem of the interaction with other active substances that are broken down by the cytochrome P450 isoenzyme CYP3A4. This results in numerous contraindications . Some medicines, such as midazolam , ergotoxins, or the neuroleptic pimozide must not be used in patients treated with atazanavir or other HIV protease inhibitors. Concomitant use of atazanavir with efavirenz , stavudine , didanosine or clarithromycin also results in changes in atazanavir plasma levels.

literature

Journal of Chemotherapy , Issue 2, 2004
Robinson BS, Riccardi KA, Gong YF, Guo Q, Stock DA, Blair WS, Terry BJ, Deminie CA, Djang F, Colonno RJ, Lin PF: BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents, in: Antimicrob Agents Chemother . , 2000, 44 (8): 2093-2099.

Web links

Patient information (English) at MedlinePlus
Chapter 38: Antiretrovirals and Essential Drugs in HIV 2010. The Book on HIV and AIDS.
Chapter 2: Substance classes, drug overview in HIV 2010. The book on HIV and AIDS.

Individual evidence

^ ^A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[MERCK_Index-1] A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.