Averages and standard deviations of transport parameters for the 24 independent replicate fits.

ak1 is the drug independent association rate constant from the membrane to P-gp. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, Fig. 3C.bT(0) is the surface density of efflux active P-gp in the apical membrane inner monolayer for all drugs. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, Fig. 3C. The units P-gp/mm2 can be converted to mmols P-gp per liter of inner apical membrane simply by dividing by 0.8 [23].ckr is the dissociation rate constant from the P-gp binding site into the apical bilayer. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, Fig. 4A.dk2 is the efflux rate constant from the P-gp binding site into the apical chamber. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, Fig. 4A.eThe partition coefficient between the cytosol and the inner plasma/apical monolayer, KPC[23]. Cell membrane partition coefficients were estimated using 0.1 mm extruded unilamellar liposomes (LUV) whose lipid compositions mimic roughly the lipid compositions of the respective membrane monolayers: inner cytosolic PS/PE/chol (1∶1∶1); apical outer, PC/SPH/chol; and basolateral outer, PC/chol (2∶1). Only the inner cytosolic partition coefficient, KPC, is shown in this table.fKC = k1/kr is the substrate binding constant from inner apical membrane monolayer to P-gp. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, data not shown. This value is calculated from the actual fitted values, rather than the average 1-digit values of k1 and kr reported in the Table.gPBA and PAB refers to the +GF120918 steady-state passive permeability coefficient, B>A and A>B respectively. These values increase initially to a final steady-state value [32], which is reported here as an average value±standard deviation over all relevant datasets.hkB and kA refers to the 1st order rate constant for transport through a bidirectional transporter for digoxin and for loperamide. The average value±standard deviation for the 24 independent replicate fits obtained for all drugs is shown, while the entire range is shown in curly brackets, Fig. 4B.iDigoxin's partition coefficients have not yet been measured. We set it to 100, as that is the lower bound for measured values.