Tipranavir

IUPAC: (all- R)-N -[3 - [1 - ( 2-hydroxy -4-oxo -6 -phenethyl -6 -propyl- 5H -pyran- 3-yl) - propyl] -phenyl]- quinolin- 8- sulfonamide

J05AE09

HIV protease inhibitor

86-89 ° C

Template: Infobox chemical / molecular formula search available

Tipranavir (trade name: Aptivus ®, manufactured by Boehringer) is a drug used to treat infected with HIV-1 patients as part of a combination antiretroviral therapy. It is included in the group of HIV protease inhibitors, but is structurally different from the other representatives of this class. The approval of an oral dosage form in the U.S. in June 2005, Europe in late 2005.

Indication and effect

Tipranavir for the treatment of HIV infection in individuals that are resistant to other HIV protease inhibitors have been developed. Because of the potential for serious adverse reactions admission " under certain conditions " (European Medicines Agency ) has been issued. Usually, tipranavir should be given in combination with ritonavir. Treatment with HIV protease inhibitors occurs within a "highly active antiretroviral therapy" (HAART ) in combination with other drugs, so-called inhibitors of reverse transcriptase (NNRTI, NRTI).

Mechanism of action and pharmacokinetics

HIV protease inhibitors to inhibit an enzyme required for the virus to produce infectious new virus particles. A reduction in viral load is due. In some cases, however, evolve relatively rapidly resistance to these agents. In contrast to the other representatives of the HIV protease inhibitors tipranavir has no peptide-like structure. It is thus the first representative of the non-peptidic HIV protease inhibitors. The differences in structure make it seem to be that this drug cross-resistance less subject than the peptidic HIV protease inhibitors and hence works against HIV strains that have developed resistance to other drugs. In such studies, strains showed a significantly superior efficacy over other tipranavir of HIV protease inhibitors. Tipranavir is taken twice a day with a meal. In the blood, tipranavir is more than 90 % bound to proteins. The drug is largely excreted by the liver via the cytochrome P450 enzyme system, mainly metabolized by CYP3A4 and over the chair. The mean plasma half-life of tipranavir is about five to six hours.

Side Effects and Risks

The superior efficacy of tipranavir against the other representatives of the HIV protease inhibitors apparently is associated with a greater risk for side effects. The discontinuation rate in the clinical studies was treated with tipranavir patients at 8 %, twice as high as in the control group ( 4%). Most frequently observed diarrhea and nausea. These are headache, abdominal pain and rashes. The combination of tipranavir / ritonavir could be toxic to the liver, especially in combination with enfuvirtide. Elevated levels of transaminases are relatively frequently observed. Therefore, tipranavir should not be used in patients with moderate or severe liver dysfunction.

The interaction profile of tipranavir with ritonavir, is complex. Responsible for this is a complicated mechanism of induction and inhibition of various metabolisation in the organism (eg, cytochrome P450 ). May not be applied at the same time the anti-tuberculosis drug rifampicin, the cholesterol-lowering drug lovastatin and simvastatin. Atorvastatin is allowed with restrictions. Also, certain benzodiazepines, oral contraceptives, and the antibiotic clarithromycin and other antiretroviral agents of change plasma levels of tipranavir.