Molecule

Drug Groups

approved; investigational

Description

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

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

External Links