Protease inhibitors

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:

• HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir etc.)
• Hepatitis C: experimental agents: BILN 2061, VX 950.

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 Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir.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. 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 .

References

• A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck