PROTEASE INHIBITORS

The protease inhibitors are extensively metabolised by cytochrome P450, particularly CYP3A4. All of the protease inhibitors inhibit CYP3A4, with ritonavir being the most potent inhibitor, followed by indinavir, nelfinavir, amprenavir, and saquinavir. The protease inhibitors therefore have the potential to interact with other drugs metabolised by CYP3A4, and are also affected by CYP3A4 inhibitors and inducers. Ritonavir and nelfinavir also affect some other cytochrome P450 isoenzymes. In addition, protease inhibitors are substrates as well as inhibitors of P-glycoprotein. The plasma level of protease inhibitors is thought to be critical in maintaining efficacy and minimising the potential for development of viral resistance. Therefore even modest reductions in levels are potentially clinically important.