Product Overview
Tipranavir is a potent HIV protease inhibitor, which has been proven effective in inhibiting the HIV protease with a Ki value of 8 pM and showing an IC90 value of 100 nM. It is believed that tipranavir can block the replication of numbers of viruses resistant to the current range of protease inhibitor. And the major amino acid substitutions of HIV-1 protease were identified to be associated with tipranavir sensitivity and resistance. As a highly potent HIV protease inhibitor, tipranavir inhibited HIV-2 protease with high potency (Ki <1 nM) and was also effective against V82A and V82F/I84V mutants (Ki 3.0 and 0.25 nM, respectively). High Ki values against other aspartyl proteases such as human pepsin, cathepsins D and E illustrated the selectivity for HIV protease. An investigation of the effect of protein binding on antiviral activity was performed in HIV-1IIIB infected cells in a medium of 10% fetal bovine serum and 75% human plasma, where above 99% of the inhibitor is protein bound and an IC90 value of 1.4 µM was observed. Additionally, a study of antiviral activities of tipranavir was operated with 134 clinical isolates in vitro, which showed the attractive properties of broadly protease inhibitor resistant HIV clinical samples. In a mouse model with 5 mg/kg tipranavir dosing, as a result, CLtot was 0.17 ±0.10 L/h/kg, Vss was 0.51 ±0.14 L/kg, and t1/2 was 5.4 ±0.3h. And following 10 mg/kg oral dosing in rats, got the result of F was 30% compared to 5 mg/kg tipranavir dosing. After being proved an effective therapeutic agent for treatment of AIDS. An evaluating of the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir was carried out in HIV-1-infected pediatric patients. The result of the evaluating indicated that the pediatric patients do well with regard to safety, tolerability and virologic efficacy when they are stable on a tipranavir-based regimen.
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