Tipranavir: a novel second-generation nonpeptidic protease inhibitor

Abstract

Tipranavir is a new nonpeptidic protease inhibitor and belongs to the class of 4-hydroxy-5, 6-dihydro-2-pyrones. Chemically, tipranavir is based on coumarin and sulfonamide compounds, amongst others. It exhibits potent and specific activity against both HIV-1 and -2. Tipranavir 500 mg in combination with ritonavir 200 mg twice daily results in optimum viral load reduction and suppresses both wild-type and protease inhibitor-resistant virus. It is metabolized by the cytochrome P4503A4 enzyme and its pharmacokinetic parameters are enhanced when combined with ritonavir. Tipranavir is excreted primarily in the feces, with minimal excretion in urine. In early trials, tipranavir/ritonavir was demonstrated to be safe and well tolerated, with mild gastrointestinal side effects. Preliminary data indicate pharmacokinetic interaction with nucleotide reverse transcriptase inhibitors; however, no dose adjustments are recommended at this time. Virologic response is not adequate when combined with other ritonavir-boosted protease inhibitors, and is currently not recommended. As with other protease inhibitors, tipranavir interacts with fluconazole, atorvastatin, clarithromycin and rifabutin and absorption is reduced when taken with antacids and didanosine (enteric coated formulation). Phase III trials are underway to compare the efficacy of tipranavir/ritonavir with other antiretroviral agents.