For oral administration twice daily, Tipranavir must be combined with a low dose of ritonavir to enhance its bioavailability. In mice co-treated with Tipranavir and ritonavir, the concentration of Tipranavir in the liver, spleen, and eyes is notably higher compared to mice treated with Tipranavir alone. Metabolites of Tipranavir constitute 31% and 38% of the composition in serum and liver, respectively, in the group treated only with Tipranavir. In contrast, in the group treated with both Tipranavir and ritonavir, only 1% and 2% of the metabolites are found in the serum and liver, respectively. Following a single dose of [14C]Tipranavir with ritonavir coadministration in Sprague-Dawley rats, the predominant metabolite identified in feces is an oxidation product, while no single metabolite predominates in the urine^[2].

Tipranavir (PNU-140690) impedes the enzymatic action and the dimerization of HIV-1 protease subunits, showing strong efficacy against a broad range of both wild-type and multiple PI-resistant HIV-1 strains. A collection of 11 clinical isolates resistant to multiple PIs but sensitive to Tipranavir undergoes rapid development of high-level resistance to Tipranavir after ten passages, demonstrating the ability to replicate even in high concentrations of Tipranavir. Specifically, cHIVBI54V and cHIVBI54V/V82T strains exhibit significant resistance to Tipranavir, with IC50 values of 2.9 and 3.2 μM, respectively, marking an 11- to 12-fold increase over the IC50 for cHIVB^[1].