TABLE 3

Estimation of the inhibitory effect of the statins on BSEP-mediated transport of TCA in humans The detailed method for calculation of these parameters is described under Materials and Methods. Cmax,u,blood (=Cmax,blood × fu,blood) represents the reported values of the maximum unbound blood concentration, and Iin,max,u represents the estimated maximum unbound concentration at the inlet to the liver. Simvastatin was administered as a lactone form. Cmax,u,blood was cited from other articles: simvastatin (Lilja et al., 1998); atorvastatin and pravastatin (Lilja et al., 1999); cerivastatin (Muck, 2000); pitavastatin (Fujino et al., 1998); and fluvastatin (Lennernas and Fager, 1997).


Statin

Atorvastatin

Cerivastatin

Fluvastatin

Pitavastatin

Pravastatin

Simvastatin
Cmax,u,blood (nM) 0.454 0.0696 4.18 1.67 58.6 0.444
Iin,max,u (nM) 14.8 0.601 27.9 10.2 2294 104
Free concentration in liver (I) (μM) 0.295 0.0120 0.557 0.204 45.9 2.08
1 + I/Ki
1.03
1.00
1.02
1.01
1.28
1.16