S1   Role of P-glycoprotein in CNS and Genital Tract Penetration

Richard Kim
Vanderbilt Univ. Sch. of Med., Nashville, TN

HIV protease inhibitors have proven remarkably effective in treating HIV-1 infection. However, some tissues such as the brain and testes (sanctuary sites) are possibly protected from exposure to HIV protease inhibitors (HIV-PIs) due to drug entry being limited by the membrane efflux transporter P-glycoprotein (P-gp, encoded by MDR1), located in the capillary endothelium. A general review of P-gp expression and function, including the recently described genetic polymorphisms in MDR1, will be followed by data on the use of P-gp inhibitors as a way to enhance HIV-PI levels in organs such as the brain. Our studies suggest that both the potency and specificity of a P-gp inhibitor are important determinants for selectively enhancing the CNS and testes entry of HIV-PIs.