BCRP inhibition interactions, in vitro to in vivo translation

PMR indicates the study was requested as a PMR.

PerpetratorIn Vitro SubstrateIC50[I]1/IC50[I]2/IC50AUC RatioCmax RatioIn Vivo VictimReference
AlectinibN/P0.113a,b49729a,bN/TcFDA (2015b)
Alectinib metabolite M4N/P2.60.2N/A
BrexpiprazolePrazosin1.160.40a,b32a,b1.12RosuvastatinFDA (2015v)
Brexpiprazole metabolite DM-3411Prazosin3.040.047N/A
CariprazineN/PWeak (value N/P)N/TFDA (2015zd)
CobimetinibEstrone-3-sulfate3.30.16a137a,bN/TFDA (2015h)
DaclatasvirGenistein10.90.21a,b30a,b1.471.84RosuvastatinFDA (2015j)
Isavuconazonium sulfateN/P920.19a,b20a,bNo effect (value N/P)MethotrexateFDA (2015i)
LesinuradMethotrexate62.7% at 100 µM<0.01N/TFDA (2015zg)
OsimertinibN/P20.063a320bN/T, PMRFDA (2015x)
RolapitantCladribine0.17210b8364a,b2.182.38SulfasalazineFDA (2015za)
SelexipagMethotrexate1.90.017a0.42aN/TFDA (2015z)
Selexipag metabolite ACT-333679Methotrexate5.6N/AN/A
SonidegibN/P1.50.98a,b783a,bN/TFDA (2015t)
  • N/P, not provided; N/T, not tested.

  • a The ratio was calculated by the University of Washington Drug Interaction Database editorial team.

  • b Values exceed the FDA cut-off value of 0.1 ([I]1/ IC50) or 10 ([I]2/IC50).

  • c A clinical study was recommended in the comments by the FDA reviewers.