Effect of potential basolateral and/or apical transporter substrates on digoxin and loperamide transport



Drug Used (1 μM)

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
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.