P-Glycoprotein and Protease Inhibitors

• All protease inhibitors are substrates of P-gp

• PIs can also inhibit P-gp to varying degrees:

  • ritonavir>nelfinavir, saquinavir

• Interest in using P-gp inhibitors to enhance protease inhibitor concentrations, particularly in sanctuary sites (e.g., CNS)

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References:

• Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101:289-94.

• Lee CGL, Gottesman MM, Cardarelli CO, et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 1998;37:3594-3601.