替拉那韦

IC50: 66-410 nM (HIV-1 isolates)

Tipranavir (PNU-140690) inhibits the enzymatic activity of HIV-1 protease, blocks the dimerization of protease subunits, and exerts potent activity against a wide spectrum of wild-type and multi-PI-resistant HIV-1 variants. When a mixture of 11 multi-PI-resistant (but TPV-sensitive) clinical isolates (HIV _11MIX ), which include HIV _B and HIV _C , is selected against Tipranavir, HIV _11MIX rapidly (by 10 passages [HIV _11MIX ^P10 ]) acquires high-level Tipranavir (PNU-140690) resistance and replicates at high concentrations of Tipranavir (PNU-140690). cHIV _B ^I54V and cHIV _B ^I54V/V82T are significantly resistant to Tipranavir (PNU-140690), with IC ₅₀ s of 2.9 and 3.2 μM, respectively, which are 11- and 12-fold increases in comparison to the IC ₅₀ against cHIV _B , respectively.

Tipranavir (PNU-140690) is administered orally twice daily and must be given in combination with low-dose ritonavir (RTV) to boost Tipranavir bioavailability. In Tipranavir/r-cotreated mice, the Tipranavir (PNU-140690) abundance in the liver, spleen, and eyes is significantly higher than that in mice treated with Tipranavir alone. Tipranavir (PNU-140690) metabolites accounts for 31 and 38% in the serum and liver in the Tipranavir-alone group. In Tipranavir (PNU-140690) and Tipranavir (TPV/r)-cotreated mice, only 1 and 2% of metabolites are detected in the serum and liver. Sprague-Dawley rats are administered a single dose of [ ¹⁴ C]Tipranavir (PNU-140690) with coadministration of RTV. The most abundant metabolite in feces is an oxidation metabolite. In urine, no single metabolite is found to be significantly present.