Kinetic analysis of P-glycoprotein-mediated doxorubicin efflux.

摘要: P-glycoprotein lowers the intracellular concentration of a variety unrelated compounds including doxorubicin by actively removing them from cell. Mathematical modeling techniques have been applied to transmembrane transport in nonresistant HL-60 cell line and P-glycoprotein-containing resistant subclone, HL-60R, obtain clearances for inward outward transport. Distribution [14C]doxorubicin extracellular fluid into pellet was analyzed with closed two-compartment system that fitted experimental measurements drug concentrations pellet, represented third compartment includes trapped along intact cells. Transmembrane diffusion clearance similar two lines (1.00 vs. 1.06 microliters sec-1), yielding an apparent permeability coefficient 7.4 x 10(-5) cm sec-1. However, total efflux averaged 0.99 +/- 0.05 sec-1 2.29 0.62 HL-60R. The estimated P-glycoprotein-mediated HL-60R 1.23 0.51 This approach provides direct estimates parameters cells should be useful studying mechanism action interactions inhibitors P-glycoprotein.