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:
- 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 Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir.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[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 [1][1][1]. |
References
- A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck
Antivirals, other than for HIV (primarily J05, also S01AD and D06BB) | |
|---|---|
| Anti-herpesvirus (DNA, I) | guanine analogues (Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir) • nucleoside analogues (Idoxuridine, Trifluridine, Vidarabine) • Cidofovir • Docosanol • Fomivirsen • Foscarnet • Tromantadine |
| HPV/MC (DNA, I) | Imiquimod • Podophyllotoxin |
| Hepatitis B (DNA, VII) | Adefovir • Interferon alfa-2b • Pegylated interferon alfa-2a • Entecavir • Lamivudine • Telbivudine • Tenofovir† |
| Hepatitis C (RNA, IV) | Pegylated interferon alpha • Ribavirin • Taribavirin† • Boceprevir† |
| Picornavirus (RNA, IV) | Pleconaril† |
| Anti-influenza agents (RNA, V) | Arbidol
adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) neuraminidase inhibitors (Oseltamivir, Zanamivir, Peramivir†) |
| HIV (Reverse, VI) | See HIV pharm |
| Other antiviral agents | general (Inosine, Interferon) |
| †Undergoing clinical trials, not FDA approved. | |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
