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Abstract
The P-glycoprotein (Pgp) protein pump is implicated in the efflux of a very significant number of drugs currently on the market. Since their creation, the efficacy of HIV protease inhibitor drugs have known to be significantly affected by Pgp efflux. This complicates the drawbacks of mainstream HIV drug treatment known as highly active antiretroviral treatment (HAART). HAART is already vulnerable to the development of HIV drug resistance, the sequestering of HIV into sanctuary sites, and overall poor oral drug bioavailability. Newer evidence suggests that in addition to being transported out of cells as P-gp substrates these drugs can also work as Pgp inhibitors, creating a more complicated and unique picture of how these drugs interact with Pgp. Four HIV protease inhibitors were selected for this study: saquinavir, ritonavir, indinavir, and lopinavir. The goal is to investigate the differences in their binding profile with Pgp and to determine how the structural differences among each of these drugs can lead to the unique Pgp interactions associated with this class of drugs.