Table 1.

The effect of SLCO1B1 polymorphism or inhibitors on AUC changes of substrate drugs

Drug	SLCO1B1 polymorphism or drug inhibitor	Simulated AUCR	Observed AUCR	R value
Rosiglitazone	Gemfibrozil	2.41	2.36	1.02
Pioglitazone	Gemfibrozil	3.84	3.2	1.20
Pitavastatin	SLCO1B1 polymorphism (c. 521 CC vs. c. 521 TT)	1.90a	3.08a	0.62a
	Gemfibrozil	1.58	1.45	1.09
	Cyclosporineb	3.29	4.55	0.72
Repaglinide	SLCO1B1 polymorphism (c. 521 CC vs. c. 521 TT)	1.88	1.83	0.97
	Gemfibrozilc	3.22	5.0	0.64
	Cyclosporineb	2.79	2.4	1.16

References in the Table and superscripts a–c are listed in Table  S2 .

AUC, area under the concentration‐time curve; AUCR, ratio of AUC; R value, ratio of the simulated AUCR and observed AUCR.

^aThe simulated ratio of SLCO1B1 c. 521 CC and SLCO1B1 c. 521 TT was compared to the observed ratio of “SLCO1B1 *15/*15 and ABCG2 421C/C 421C/A” (mixed with BCRP polymorphism) and “SLCO1B1 *1b/*1b and ABCG2 421C/C” because no purely genotyped “SLCO1B1 *15/*15 and ABCG2 421C/C” data were reported. ^bThe estimated cyclosporine K _i values of OATP1B1/1B3 (0.014/0.007 μΜ) were used with updated unbound fraction = 0.1 (Product Labeling: Drugs@FDA). ^cThe physiologically based pharmacokinetic models with gemfibrozil‐glucuronide K _Ioatp1b of 7.9 μM underestimated the complex repaglinide‐gemfibrozil drug‐drug interactions, as also observed in literature. The simulated AUCRs were 3.79 and 5.15 if K _Ioatp1b of 7.9 μM was reduced to the values of 4 μM and 1.48 μM, respectively.