Drug-drug interaction (DDI) indices estimated from in vitro OATP4C1-mediated T3 uptake inhibition kinetics by therapeutic drugs

IC50 (µM) are shown as mean ± S.E., and fmax,u (%) is the unbound fraction of the drugs. Data for Cmax and fmax,u (%) of the drugs are taken from previous reports. The DDI indices were determined using the inhibition constant (IC50) with the maximum plasma concentration (Cmax; bound plus unbound) ([I]max) and the maximum unbound concentration (Cmax,u) ([I]max,u) of the drugs following the regulatory guidelines described in the text.

DrugIC50 (µM)Cmax (µM)Cmax,u (µM)fmax,u (%)DDI index
[I] = [I]max[I] = [I]max,u
Levofloxacin420 ± 15019a14.174a0.0450.033
Ritonavir8.5 ± 1.416b0.161b1.90.019
Quinidine100 ± 1119c1.910c0.190.019
Saquinavir4.3 ± 0.63.7b0.0742b0.860.0172
Clarithromycin200 ± 163.8d1.950d0.0190.0095
Crizotinib24 ± 81.1e0.0999e0.0460.0041
Spironolactone53 ± 70.48f0.04810f0.00910.00091
Fluvastatin41 ± 80.65g0.0335g0.0160.00079
Nicardipine51 ± 80.27h0.02710h0.00530.00053
Verapamil110 ± 220.51i0.05110i0.00460.00046
  • a Values obtained from Rodvold and Neuhauser (2001).

  • b Values obtained from Hsu et al. (1998).

  • c Values obtained from Capucci et al. (1998).

  • d Values obtained from Rodvold (1999).

  • e Values obtained from Fujiwara et al. (2016).

  • f Values obtained from Overdiek et al. (1985).

  • g Values obtained from Scripture and Pieper (2001).

  • h Values obtained from Forette et al. (1985).

  • i Values obtained from Krecic-Shepard et al. (2000).