| Item |
Information |
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Drug Groups
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approved; investigational |
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Description
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Tipranavir is a sulfonamide-containing dyhydropyrone and a nonpeptidic protease inhibitor that targets the HIV protease. It is administered with ritonavir in combination therapy to treat HIV infections. |
| Indication |
For combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. |
| Pharmacology |
Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. |
| Toxicity |
Oral LD50 in rat is over 5,000 mg/kg. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin. |
| Affected Organisms |
| • |
Human Immunodeficiency Virus |
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| Biotransformation |
Hepatic. In vitro metabolism studies with human liver microsomes indicated that CYP 3A4 is the predominant CYP enzyme involved in tipranavir metabolism. |
| Absorption |
Absorption is limited, although no absolute quantification of absorption is available. |
| Half Life |
5-6 hours |
| Protein Binding |
Extensive (> 99.9%), to both human serum albumin and α-1-acid glycoprotein. |
| References |
| • |
Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG: Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 2005 Oct;68(1):27-35.
[Pubmed]
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Tipranavir: PNU 140690, tipranivir. Drugs R D. 2006;7(1):55-62.
[Pubmed]
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Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7.
[Pubmed]
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| • |
Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18.
[Pubmed]
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| External Links |
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