Table 5

Category II: lack of concordance among the in vitro Pgp assays

ClassEAC ResultNumber of CompoundsMean Papp A → BMedian PappA → BRange of Papp A → BRemarks
nm/s
IIA nontransported substratesNYY10535598316–714Very high PappA → B
10/10 with Papp >300 nm/s
Conclusion: region of low resolution for efflux assay
IIB1 transported substratesYNN1314.69.541.91–44.9Very low Papp A → B
10/13 with Papp <20 nm/s
0/13 with Papp >300 nm/s
Conclusion: region of poor response for ATPase and calcein-AM
IIB2 transported substratesYYN720.410.20.94–73.9Very low Papp A → B
6/7 Papp <20 nm/s
0/7 with Papp >300 nm/s
Conclusion: Additional region of poor response for calcein-AM
IIB3 YNY115.9Cyclosporin A
IICNYN0Not observed

n = 31 of 66 compounds. See Experimental Procedures for the details of each assay.

  • 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.