Effect of potential basolateral and/or apical transporter substrates on digoxin and loperamide transport
Compound | Transportera | Drug Used (1 μM) | References | ||
|---|---|---|---|---|---|
| Loperamide | Digoxin | ||||
| Benzbromarone | hMRP1-6, hURAT1 | Not tested | No effectb with 10 μMc | Enomoto and Endou, 2005; Iwanaga et al., 2005 | |
| Digoxind | oatp1a4,4c1,1b3,1b1, roatp2, rOat-K2 | moderate inhibition with 10 μM DGX | NA | Dresser et al. 2001 | |
| Fexofenadined | hOAT3, roatp3, | 300 μM inhibits after 4 h | No effect with 300 μM | Tahara et al., 2006 | |
| Glycyrrhizic acid | hOATP1B1,1B3, roatp1a1, 1a4, 1b2 | Not tested | No effect with 200 μM | Ismair et al., 2003 | |
| Indocyanine green | rOat2, 3, r/hOATP2 | Not tested | No effect with 10 μM | Morita et al., 2001 | |
| Loperamided | N.A.e | Good Inhibition | |||
| Mitoxantronef | MRP1, BCRP | No effect with 25 μM | No effect with 25 μM | Morrow et al., 2006; Pan and Elmquist, 2007 | |
| Ouabain | rOatK-2, roatp2, oatp4c1, 1b3 | 10 μM inhibits after 4 h | 10 μM shows biphasic curvegc | Dresser et al., 2001 | |
| PAH | m/r Oat1, hOAT1, rOat2,3 | No effect with 100 μM | 100 μM PAH inhibits after 3 h | Dresser et al., 2001; Kikuchi et al., 2004 | |
| Probenecid | m/r Oat1,3,4, hOAT1, rOat-K2 | No effect with 200 μM | No effect with 200 μM | Dresser et al., 2001; Sugiyama et al., 2001; Horikawa et al., 2002 | |
| Rifamycing | rOat2, hOATP-A, C, 8, 1B1, 1B3 | Not tested | No effect with 3 μM | Dresser et al., 2001; Vavricka et al., 2002 | |
| Taurocholic acid | Bile acid/salt transporters ASBT, BSEP, NTCP | No effect with 200 μM | No effect with 200 μM | Harris et al., 2004; Mita et al., 2006 | |
| Tetraethylammonium | Many OCTs | No effect | Not tested |
Dresser et al., 2001
| |
N.A., not applicable; URAT, uric acid transporter; PAH, para-aminohippurate.
↵ a The compounds used here are substrates and/or inhibitors of known mammalian transporters. Names of all human (h) transporters (OATs, OATPs, and MRPs) are in upper case. Transporters in mice (m) or rats (r) are in all lower case (e.g., oatp) or start with an upper case letter and the rest are in lower case (e.g., Oat).
↵ b No effect means lack of significant (>10%) inhibition by 2 h.
↵ c Benzbromarone at 100 and 200 μ M was tested, but these concentrations had toxic effects on cells.
↵ d Digoxin, loperamide, and fexofenadine are P-gp substrates.
↵ e Mitoxantrone is an inhibitor of bcrp1/ABCG2
↵ f The best inhibition is seen when there is digoxin transport in the presence of ouabain without any preincubation; 30 min of preincubation with ouabain produced a jump at 4 h in two separate experiments.
↵ g Rifampicin is a P-gp inducer.