Compounda | % FA | Papp (A-B) | Papp (B-A) | ER (MDCK Bcrp ERb) | Pappi (A-B) | Pappi (B-A) | ERi | TSIPapp (A-B) | TSIPapp (B-A) | TSIER | AQ | Plasma AUC or Concentration Ratio (KO/WT)c |
---|---|---|---|---|---|---|---|---|---|---|---|---|
×10−6 cm/s | ×10−6 cm/s | |||||||||||
Major substrate | ||||||||||||
Cerivastatin | 98 | 5.4 | 5.0 | 0.9 | 8.8 | 3.1 | 0.4 | 64 | 37 | 62 | 0.4 | |
Erythromycin | 35 | 0.4 | 3.0 | 8.1 (8.5) | 0.6 | 1.7 | 2.7 | 72 | 43 | 67 | ||
Etoposide | 25 | 0.5 | 6.8 | 12.7 (9.7) | 1.1 | 3.4 | 3.1 | 106 | 49 | 75 | ||
Fluvastatin | 98 | 2.1 | 10.3 | 4.9 | 4.7 | 3.9 | 0.8 | 123 | 63 | 83 | 0.6 | |
Furosemide | 61 | 0.6 | 9.7 | 17.5 | 1.6 | 4.5 | 2.8 | 190 | 53 | 84 | ||
Irinotecan | N.A. | 1.4 | 5.0 | 3.7 | 2.3 | 3.9 | 1.7 | 66 | 23 | 54 | 0.4 | |
Nitrofurantoin | 100 | 0.8 | 18.8 | 24.1 | 4.0 | 7.2 | 1.8 | 409 | 61 | 92 | 0.8 | 4 |
Norfloxacin | 40 | 1.9 | 5.6 | 3.0 | 2.7 | 3.2 | 1.2 | 44 | 43 | 61 | 0.3 | |
Rosuvastatin | 20 | 0.5 | 7.5 | 15.9 | 0.9 | 6.8 | 7.9 | 82 | 10 | 50 | ||
Sulfasalazine | 13 | 0.8 | 13.4 | 16.9 | 1.5 | 9.7 | 6.4 | 91 | 28 | 62 | 111 | |
Teniposide | 0 | 0.8 | 8.8 | 10.8 | 1.5 | 8.2 | 5.4 | 84 | 8 | 50 | ||
Topotecan | 30 | 1.0 | 7.1 | 6.9 (2.4) | 2.4 | 3.9 | 1.6 | 130 | 45 | 76 | 0.6 | 6 |
Partial substrate | ||||||||||||
Ciprofloxacin | 69 | 2.5 | 5.2 | 2.1 | 2.8 | 3.9 | 1.4 | 12 | 26 | 34 | 0.1 | 2 |
Daunorubicin | 10 | 0.4 | 2.1 | 4.9 | 0.5 | 1.6 | 3.3 | 9 | 27 | 33 | ||
Imatinib | 67 | 3.7 | 6.0 | 1.6 | 5.9 | 5.6 | 1.0 | 59 | 6 | 41 | 0.4 | 1.3 |
Prazosin | 100 | 6.2 | 11.1 | 1.8 | 6.7 | 8.0 | 1.2 | 9 | 28 | 34 | 0.1 | |
Zidovudine | 90 | 6.7 | 9.6 | 1.4 | 7.4 | 7.1 | 1.0 | 10 | 26 | 33 | 0.1 | 0.97 |
Nonsubstrate | ||||||||||||
Actinomycin D | 5 | 0.7 | 4.5 | 6.4 | 0.4 | 8.2 | 5.4 | 115 | −82 | 15 | ||
Colchicine | 44 | 0.9 | 6.6 | 7.6 | 0.9 | 5.6 | 6.4 | 1 | 16 | 16 | ||
Digoxin | 68 | 0.9 | 12.6 | 14.6 (1.3) | 0.9 | 10.4 | 11.8 | 2 | 17 | 19 | ||
Metolazoned | 64 | 2.9 | 9.6 | 3.3 (5.1) | 3.4 | 8.2 | 2.4 | 16 | 15 | 27 | ||
Paclitaxel | 6 | 0.4 | 9.1 | 21.4 | 0.3 | 8.3 | 25.3 | −23 | 9 | −18 | ||
Saquinavir | 4 | 0.5 | 5.6 | 11.0 | 0.5 | 5.6 | 11.1 | −2 | 1 | −1 | ||
Vinblastine | 5 | 1.0 | 13.2 | 13.5 (1.8) | 0.9 | 12.3 | 14.0 | −11 | 7 | −4 | ||
Vincristine | <10 | 0.9 | 3.5 | 4.2 | 0.9 | 3.3 | 3.5 | 11 | 6 | 15 |
N.A., not applicable.
↵a BCRP substrate and nonsubstrate reference source: Merino et al. (2005) and Choudhuri and Klaassen (2006).
↵b ER from MDCK Bcrp bidirectional assay was given in parentheses, where ER ≥ 2 is considered as the boundary for substrates.
↵c Pharmacokinetic data after oral administration from Bcrp KO versus WT mice. The in vivo reference source: Jonker et al. (2002); Zaher et al. (2006); Merino et al. (2005, 2006); Giri et al. (2008); and Oostendorp et al. (2009).
↵d False-negative substrate.