Abstract

HIV-1 protease inhibitors are an important part of the arsenal for the treatment of AIDS. Currently available protease inhibitors are known to interact with CYP3A4. Consequently, they are highly prone to drug-drug interactions with other coadministered drugs that are substrates or inhibitors of CYP3A4. Thus, development of newer HIV-1 protease inhibitors with a lower tendency for drug-drug interactions would be advantageous. We have compared the CYP450 inhibitory profiles of several discovery phase HIV-1 protease inhibitor candidates with saquinavir, indinavir, nelfinavir, and a structurally related compound, PNU 140690.The data indicate that discovery phase compounds have a different inhibitory profile than the other test compounds and show a lower potential for CYP3A4 and CYP2D6 based drug-drug interactions. However, they have a higher potential for CYPlA2 and CYP2C9 based drug-drug interactions. None of the compounds tested inhibited CYP2El or CYP2A6 to any significant extent.