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.
| Drug | IC50 (µM) | Cmax (µM) | Cmax,u (µM) | fmax,u (%) | DDI index | |
|---|---|---|---|---|---|---|
| [I] = [I]max | [I] = [I]max,u | |||||
| Levofloxacin | 420 ± 150 | 19a | 14.1 | 74a | 0.045 | 0.033 |
| Ritonavir | 8.5 ± 1.4 | 16b | 0.16 | 1b | 1.9 | 0.019 |
| Quinidine | 100 ± 11 | 19c | 1.9 | 10c | 0.19 | 0.019 |
| Saquinavir | 4.3 ± 0.6 | 3.7b | 0.074 | 2b | 0.86 | 0.0172 |
| Clarithromycin | 200 ± 16 | 3.8d | 1.9 | 50d | 0.019 | 0.0095 |
| Crizotinib | 24 ± 8 | 1.1e | 0.099 | 9e | 0.046 | 0.0041 |
| Spironolactone | 53 ± 7 | 0.48f | 0.048 | 10f | 0.0091 | 0.00091 |
| Fluvastatin | 41 ± 8 | 0.65g | 0.033 | 5g | 0.016 | 0.00079 |
| Nicardipine | 51 ± 8 | 0.27h | 0.027 | 10h | 0.0053 | 0.00053 |
| Verapamil | 110 ± 22 | 0.51i | 0.051 | 10i | 0.0046 | 0.00046 |
↵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).