TABLE 6

Hepatic OATP inhibition interactions, in vitro to in vivo translation

PerpetratorOATPIn Vitro SubstrateIC50Dose CmaxCmax/IC50In Vivo VictimAUC RatioReference
μMmgμM
Fluticasone1B1N/S0.20.81.95 × 10−4<0.1 (0.001a)(FDA, 2013d)
Macitentan1B1Atorvastatin6.9100.60.087a(FDA, 2013s)
1B3Estrone-3-sulfate140.043a
Sofosbuvir1B3Fluo-3203.54002.0<0.1 (0.01a)(FDA, 2013v)
Trametinib1B1Estradiol 17-β-glucuronide1.320.040.031(FDA, 2013p)
1B3Estradiol 17-β-glucuronide0.940.043
Dabrafenib1B1N/S1.41502.842.03bN/T, Rc = 1.0(FDA, 2013w)
1B3N/S4.70.60bN/T, Rc = 1.0
Simeprevir1B1Estradiol 17-β-glucuronide0.2620014.555.9a,bRosuvastatin2.8(FDA, 2013r)
Atorvastatin2.2
Simvastatin1.7
  • N/T, not tested in NDA reviews; N/S, not specified; fu, fraction unbound; Iin,max, maximum [inhibitor] at liver inlet, if R ≥ 1.25, in vivo study is warranted.

  • a Value computed by the DIDB Editorial Team.

  • b Underlined values exceed FDA cut-off (0.1) to warrant further investigation.

  • c R = 1 + (fu × Iin,max/IC50).