Table 4

Category I: concordance among in vitro Pgp assays

ClassEAC ResultNumber of CompoundsMean Papp A → BMedian Papp A → BRange of Papp A → BRemarks
Unambiguous nonsubstratesNNN1424099.89.53–8427/14 with Papp <20 nm/s
5/14 with Papp >300 nm/s
Conclusions: nonsubstrates or possible combination of low assay responses and affinity for Pgp
Unambiguous substratesYYY181311023.01–4133/18 with Papp <20 nm/s
1/18 with Papp >300 nm/s
Conclusions: optimal combination of assay responses and affinity for Pgp
InhibitorsNNY35597582.12–916e.g., GF120918

n = 35 of 66 compounds. See Experimental Procedures for the details of each assay.

  • Definitions: EAC: E, monolayer efflux; A, drug-stimulated ATPase; C, calcein-AM. Results are reported as yes (Y) or no (N). For efflux, yes = substrate and no = nonsubstrate; for ATPase assays, yes = stimulator and no = no activity; and for calcein-AM assay, yes = response >10% maximum fluorescence and no = response <10% maximum fluorescence.