TABLE 5

Predicted and observed AUC ratios (AUCRs) with rifampicin, trimethoprim, clopidogrel and gemfibrozil based upon inhibition of OATP1B1 and/or CYP2C8

Observed AUCRs are presented as mean (95% confidence interval), and predicted AUCRs were calculated by Eq. (2), the detail data used for this calculation are presented in Table 4.

SubstratesCoadministered drugs
Namefm,CYP2C8aRifampicin 600 mgTrimethoprim 200 mgClopidogrel 300 mgGemfibrozil 600 mg
Observed AUCRPredicted AUCRObserved AUCRPredicted AUCRObserved AUCRPredicted AUCRObserved AUCRPredicted AUCR
OATP1B1bCYP2C8bOATP1B1bCYP2C8bOATP1B1/CYP2C8bOATP1B1bCYP2C8bOATP1B1/CYP2C8b
Pitavastatin0.005.10 (3.89, 6.31)3.700.99 (0.80, 1.18)1.001.09 (0.87, 1.31)1.111.001.111.391.001.39
Pioglitazone0.681.03 (0.95, 1.11)1.001.26 (1.11, 1.42)1.132.01 (1.56, 2.46)1.002.592.593.2c (2.7, 3.8)1.392.853.97
Repaglinide0.712.78 (2.05, 3.53)3.701.99 (1.45, 2.52)1.143.09 (2.12, 4.06)1.112.783.095.0d (4.2, 5.8)1.393.114.32
Cerivastatin0.613.701.111.112.232.473.9e (2.8, 4.9)1.392.393.33
  • —, not reported.

  • a In vitro data; pitavastatin (Fujino et al., 2003), pioglitazone (Jaakkola et al., 2006), repaglinide (Kajosaari et al., 2005a), cerivastatin (Shitara et al., 2004).

  • b Inhibition pathways for the prediction of AUCR

  • c Aquilante et al. (2013)

  • d Honkalammi et al. (2011a)

  • e Backman et al. (2002)