Amprenavir

Structural formula
General
Non-proprietary name	Amprenavir
other names	Tetrahydrofuran-3-yl [3 - [(4-aminophenyl) -sulfonyl- (2-methylpropyl) amino] -1-benzyl-2-hydroxypropyl] aminomethanoate ( IUPAC ) ( 3S ) -Tetrahydro-3-furanyl- N - [(1 S , 2 R ) -3- (4- amino - N -isobutylbenzenesulfonamido) -1-benzyl-2-hydroxypropyl] carbamate
Molecular formula	C 25 H 35 N 3 O 6 S
External identifiers / databases
CAS number 161814-49-9 EC number 827-179-5 ECHA InfoCard 100.262.589 PubChem 65016 ChemSpider 58532 DrugBank DB00701 Wikidata Q422198
Drug information
ATC code	J05 AE05
Drug class	Antiviral , HIV protease inhibitor
Mechanism of action	Inhibition of HIV protease
properties
Molar mass	505.63 g · mol -1
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 .

Amprenavir (trade name: Agenerase , manufacturer GlaxoSmithKline ) is a drug from the group of HIV protease inhibitors and is used to treat HIV infections. HIV protease inhibitors are combined with other antiretroviral agents in what is known as “highly active antiretroviral therapy” ( HAART ).

history

Amprenavir was developed by Vertex Pharmaceuticals and presented to the public in 1995 as a new antiviral agent. It was approved for the USA in April 1999, and the European Medicines Agency recommended approval in October 2000.

indication

Amprenavir, like the other active substances from the group of HIV protease inhibitors, is used in combination with other antivirals to treat an infection caused by HIV-1 in adults and children over four years of age. Different combinations showed a significant decrease in viral load in about half of the patients.

Mechanism of action

Amprenavir is an inhibitor of the HIV-1 viral protease ( HIV protease ). This enzyme plays a crucial role in the formation of new infectious virus particles. Thus, by inhibiting the protease, the virus spread in the human body can ultimately be restricted. In contrast to older representatives of the same group, the binding mechanism between enzyme and active ingredient is likely to be different. This can be concluded from the fact that patients who were resistant to an older HIV protease inhibitor did not experience cross-resistance to amprenavir.

In the clinical trial phase, the effectiveness of amprenavir was compared with that of the tried and tested drug indinavir . Amprenavir appeared to be less effective and less sustainable than the comparison agent.

pharmacology

Amprenavir is given orally and is rapidly and almost completely absorbed from the gastrointestinal tract . Concomitant food consumption may have a minor effect on absorption. The elimination half-life is about 10 hours. Consequently, it is sufficient to take the drug twice a day, with a single dose of 1200 mg. About 90% of the active ingredient is bound to plasma proteins in the blood and is almost completely metabolized in the liver .

Side effects and contraindications

Adverse effects that are observed primarily affect the gastrointestinal tract . As with other HIV protease inhibitors, diarrhea and abdominal pain will occur. Next there is paresthesia , and skin reactions. Maculopapular rashes occurred in clinical studies in up to a third of patients, with life-threatening complications, such as Stevens-Johnson syndrome , occurring relatively often (in 1% of those treated) , whereupon treatment had to be discontinued. Metabolic disorders, including fat redistribution phenomena, have also been observed with amprenavir. However, this seems to be the case less frequently than with therapy with indinavir. Due to its chemical structure, amprenavir belongs to the sulfonamides . In certain cases this can lead to hypersensitivity reactions .

The mechanism of breakdown of amprenavir by the liver (mainly CYP3A4 ) results in numerous drug interactions with other drugs. In particular, lipophilic drugs that work in the CNS , such as benzodiazepines or antidepressants , but also antihistamines and antiarrhythmics , together with amprenavir, can cause serious side effects. Even with inducers of cytochrome P450 system, such as St. John's wort - extracts , caution should be exercised, as such reduce amprenavir levels in blood.

Other Information

Amprenavir is the actual active ingredient in fosamprenavir .

further reading

• Deutsche Apotheker Zeitung No. 17 (April 23, 2009)
• Wensing AM, van Maarseveen NM, Nijhuis M: Fifteen years of HIV protease inhibitors: raising the barrier to resistance . In: Antiviral Res . . October 2009. doi : 10.1016 / j.antiviral.2009.10.003 . PMID 19853627 .
• Kovalevsky AY, Ghosh AK, Weber IT: Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir . In: J Med Chem . . 51, No. 20, October 2008, pp. 6599-603. doi : 10.1021 / jm800283k . PMID 18808097 . PMC 2771923 (free full text).

Individual evidence

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.
2. ↑ AGES-PharmMed, as of November 2009.
3. ↑ Wlodawer A, Vondrasek J: Inhibitors of HIV-1 protease: a major success of structure-assisted drug design . In: Annu Rev Biophys Biomol Struct . 27, 1998, pp. 249-84. doi : 10.1146 / annurev.biophys.27.1.249 . PMID 9646869 .
4. ↑ ^{a b} Fung HB, Kirschenbaum HL, Hameed R: Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor . In: Clin Ther . 22, No. 5, May 2000, pp. 549-72. doi : 10.1016 / S0149-2918 (00) 80044-2 . PMID 10868554 .
5. ↑ ^{a b c d} Noble S, Goa KL: Amprenavir: a review of its clinical potential in patients with HIV infection . In: Drugs . 60, No. 6, December 2000, pp. 1383-410. PMID 11152018 .

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