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

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

Precipitant[I2]DoseBCRP ParametersOther Possible Intestinal Interactions
KiIC50[I2]/IC50In Vivo PK–Based DDI DataTransporter/EnzymeIC50[I2]/IC50In Vivo PK–Based DDI Data
Lapatiniba5300b1250 mg QD (SS)10.025 CIM2210,000cDecreased TOP clearance, −183% (renal, −22%)2; SN-38 +45% AUC4P-gp1.553500Digoxin AUC +2.8-fold1
CYP3A396140Midazolam AUC +45% (oral), +22% (i.v.)1
Sulfasalazinea40,0003- to 4-g SD70.46 E3S887,000No effect with MTX9; however, in vivo substrate10OATP2B131113,000
Regorafeniba1300160 mg (SS)120.0447 TOP1328,000No inhibition data14P-gp0.8131600
UGT1A1613210SN-38 glucuronide AUC +44% (when coadministered with irinotecan)13
Curcumine22,0002-g SD100.7 SSZ101.6 SSZ1014,000SSZ exposure increased significantly10P-gp∼20151100Talinolol AUC +33%–54%17,18
Erlotiniba1500150 mg QD × 21 days190.15200.13 E3S2012,000No effect on TOP21P-gp220760
CYP3A42.56d,226002-fold increase in exposure of OSI-93025; everolimus AUC +21%26; case report of toxicity with simvastatin27
CYP3A580c,23192-fold increase in exposure of OSI-93025; everolimus AUC +21%26; case report of toxicity with simvastatin27
UGT1A11.28d,241200No effect on irinotecan/SN-3828
Elacridara2800400 mg BID × 3 days290.31 MIT309200TOP AUC +143%31P-gp0.015632180,000Doxorubicin AUC +46%29; TOP AUC +143%31; paclitaxel AUC increased34
Nilotiniba2800400 mg BID × 15 days350.69 MTX361.382000No inhibition dataP-gp1.7351700
CYP3A40.4377100Midazolam AUC +30%35
Gefitiniba2000225 mg QD × 14 days391.01 E3S402000No inhibition dataCYP3A49.6d,22210No effect on docetaxel41 or everolimus42
Sunitinib50050 mg QD × 28 days430.32 E3S440.64780No inhibition data; in vivo substrate45P-gp15.2d,4433Docetaxel AUC +44.7%47; case report of toxicity with colchicine48
CYP3A419.0d,4626Docetaxel AUC +44.7%47
Pantoprazolea37040-mg SD495.5 MTX5067SSZ AUC +83.3% with 421A/C genotype51; case report of toxicity with MTX52P-gp17.95321No effect on digoxin55,56
CYP3A4154370No effect on carbamazepine,57 nifedipine,58,59 or tacrolimus60
Rabeprazole44040 mg QD × 8 days618.5 MTX5052Delayed MTX elimination50CYP3A44.95491No effect on tacrolimus62