Protease inhibitors

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For natural protease inhibitors, please see protease inhibitor (biology)

Protease inhibitors (PIs) are a class of medication used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:

Given the specificity of the target of these drugs there is the risk, as in antibiotics, of the development of drug-resistant mutated viruses. To reduce this risk it is common to use together different drugs aimed at different targets.

Antiretrovirals

Protease inhibitors were the second class of antiretroviral drugs developed. In all cases, patents remain in force until 2010 or beyond.

Name Trade name Company Patent Notes
Saquinavir Fortovase, Invirase Hoffmann–La Roche U.S. Patent 5,196,438  It was the first protease inhibitor approved by the FDA (December 6, 1995).
Ritonavir Norvir Abbott Laboratories U.S. Patent 5,541,206  -
Indinavir Crixivan Merck & Co. U.S. Patent 5,413,999  -
Nelfinavir Viracept Japan Tobacco U.S. Patent 5,484,926  -
Amprenavir Agenerase GlaxoSmithKline U.S. Patent 5,585,397  The FDA approved it April 15, 1999, making it the sixteenth FDA-approved antiretroviral. It was the first protease inhibitor approved for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200mg, delivered in eight very large gel capsules. Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir.
Lopinavir Kaletra Abbott - Is only marketed as a combination, with ritonavir.
Atazanavir Reyataz - - -
Fosamprenavir Lexiva GlaxoSmithKline - Is a pro-drug of amprenavir. The FDA approved it October 20, 2003. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reduces the number of pills required versus standard amprenavir.
Tipranavir Aptivus Boehringer-Ingelheim - Also known as tipranavir disodium
Darunavir Prezista Tibotec - It was approved by the Food and Drug Administration (FDA) on June 23, 2006. Several ongoing phase III trials are showing a high efficiency for the PREZISTA/rtv combination being superior to the lopinavir/rtv combination for first-line therapy[1]. Darunavir is the first drug in a long time that didn't come with a price increase. It leapfrogged two other approved drugs of its type, and is matching the price of a third [2][3][4].

References

  1. Darunavir-ritonavir more effective than Lopinavir-ritonavir in HIV infected, treatment-experienced patients,The Lancet, Volume 370, Number 9581, 07 July 2007, http://www.thelancet.com/journals/lancet/issue?volume=370&issue=9581
  2. Liz Highleyman, Patient Advocates Commend Pricing of New PI Darunavir, http://www.hivandhepatitis.com/recent/2006/ad1/063006_a.html
  3. [Darunavir - first molecule to treat drug-resistant HIV, http://www.news-medical.net/?id=19211]
  4. [Retaining Efficacy Against Evasive HIV, http://pubs.acs.org/cen/news/84/i34/8434drugdesign.html]
  • A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck
de:Protease-Inhibitor

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