TABLE 6

In vitro and in vivo data and considerations for potential systemic BCRP inhibitors

IC50 and Ki values are presented as reported in the respective references, along with the substrate used.

Precipitant[I1] (Cmax)Plasma BindingDoseBCRP ParametersOther Possible Systemic Interactions
KiIC50[I1]/IC50In Vivo PK–Based DDI DataTransporter/ EnzymeIC50[I1]/IC50In Vivo PK–Based DDI Data
μM%μMμM
Regorafenib8.1199.51160 mg (SS)10.0447 TOP2180No published inhibition data3P-gp0.8210
CYP3A422.2a,20.36
CYP2C81.2a,26.8
CYP2C99.4a,20.86
CYP2B610.4a,20.78
CYP2C1932.8a,20.25
UGT1A1621.4SN-38 glucuronide AUC +44% (when coadministered with irinotecan)2
UGT1A94.221.9
Sulfasalazine794>99.743- to 4-g SD40.46 E3S5170No effect with MTX6; however, in vivo substrate7OATP1B10.568140
OATP1B31286.6
OATP2B13826
Lapatinib4.2b,9>9991250 mg QD (SS)90.025 CIM10170cDecreased TOP clearance, –18% (renal, –22%)11; SN-38 +45% AUC12P-gp1.5132.8Digoxin AUC +2.8-fold9
OATP1B14101.0SN-38 AUC +45%12
CYP3A39140.11Midazolam AUC +45% (oral), +22% (i.v.)9
CYP2D613.8140.30
CYP2C81.2a,143.5Paclitaxel AUC +23%8
CYP2C911.8140.36
CYP2C1927.2140.15
Erlotinib6.06159015150 mg QD × 21 days150.15 E3S160.13 E3S1647No effect on TOP17P-gp2163.0
OATP1B12180.29
OATP1B34480.14
OATP2B10.55811
CYP3A42.56a,182.42-fold increase in exposure of OSI-93023; everolimus AUC +21%24; case report of toxicity with simvastatin25
CYP3A580a,190.082-fold increase in exposure of OSI-93023; everolimus AUC +21%24; case report of toxicity with simvastatin25
CYP2D637%d20
CYP2C88.04a,180.75No effect on paclitaxel26
CYP2C949%d20Case report of increased INR with warfarin27
CYP1A230%d20
CYP2C1942.9210.14
UGT1A11.28a,224.7No effect on irinotecan/SN-3828
Nilotinib4.3299829400 mg BID × 15 days290.69 MTX301.383.1No inhibition dataP-gp1.7292.5
OCT12.92310.47
OCT2>3031
OCT30.345314.0
CYP3A40.43211Midazolam AUC +30%29
CYP2C80.42111
CYP2C90.264a,2916No effect on S-warfarin34
CYP2D62.92a,291.5
CYP2C197.64a,290.56
UGT1A10.28a,3315
UGT1A77.8a,330.55
Pantoprazole6.535983540-mg SD355.5 MTX361.2Sulfasalazine AUC +83.3% (N.S.) with 421A/C genotype37; case report of toxicity with MTX38P-gp17.9390.36No effect on digoxin44,45
OATP1B154%d40
CYP3A41416.5No effect on carbamazepine,46 nifedipine,47,48 or tacrolimus49
CYP2D615410.43No effect on metoprolol50
CYP2C913.0a,420.50No effect on S-warfarin51 or diclofenac52,53
CYP2C194.1430.46No effect on phenytoin54,55 or diazepam56
CYP2B6200410.03
Elacridar0.32757Not available400 mg BID × 3 days570.31 MIT581.1TOP (i.v.) AUC +143%59P-gp0.01566021Doxorubicin AUC +46%57; TOP (i.v.) AUC +143%59; paclitaxel AUC increased63
OATP1B1<<2061
OATP1B3>208
OATP2B1<208
CYP3A44.9620.07
CYP2C919.1620.02
CYP1A216620.02
CYP2C192.05620.16
Gefitinib0.8649064225 mg QD × 14 days641.01 E3S650.79No inhibition dataCYP3A49.6a,180.08No effect on docetaxel66 or everolimus67
CYP2D613.8210.06Metoprolol AUC +49.5%68
CYP2C817.4a,180.05
CYP2C1936620.02