TABLE 1

DDI risk assessment based on IC50 values from uptake/efflux directions and plasma unbound Cmax

IC50 values were estimated by nonlinear regression analysis and are given as means ± S.D.

InhibitorIC50, MATE1Cmax,uMetformin AUC ChangeCmax,u/IC50, Metfromin
MPP+Metformin
UptakeEffluxUptakeEffluxUptakeEfflux
μM%
Pyrimethamine*0.492 ± 0.0391.19 ± 0.0610.313 ± 0.0520.502 ± 0.0580.29835.3–1700.950.59
Cimetidine*4.43 ± 0.0543.8 ± 0.132.56 ± 0.046.12 ± 0.0777.7446.2–54.23.01.3
Trimethoprim*8.16 ± 0.0684.5 ± 0.0874.13 ± 0.0911.3 ± 0.138.8821.5–68.62.20.79
Quinidine*6.77 ± 0.0815.5 ± 0.0945.82 ± 0.065.00 ± 0.121.34No data0.230.27
Ondansetron*0.797 ± 0.0250.935 ± 0.150.436 ± 0.0830.624 ± 0.190.0471210.110.076
Famotidine*1.670 ± 0.0310.7 ± 0.120.905 ± 0.0463.11 ± 0.1212.71.10.32
Dolutegravir7.12 ± 0.08523.8 ± 0.233.04 ± 0.0869.07 ± 0.300.18078.9–1450.0590.020
Vandetanib3.36 ± 0.063.52 ± 0.172.39 ± 0.0341.60 ± 0.130.10273.30.0430.064
Cephalexin2614 ± 0.02>10,0002110 ± 0.043>10,00069.323.90.033N.A.
Ranolazine88.1 ± 0.043111 ± 0.09248.7 ± 0.06166.3 ± 0.311.8538.5–830.0380.028
Lansoprazole60.1 ± 0.049148 ± 0.2244.0 ± 0.05666.5 ± 0.240.088311.80.00200.0013
Cobicistat5.29 ± 0.08712.2 ± 0.112.75 ± 0.0835.27 ± 0.230.054No data0.0200.010
  • Cmax,u, plasma unbound Cmax; N.A., not applicable.

  • * IC50 values obtained by uptake assay were from Lechner et al. (2016).