Table 3.

Examples of the effect of disease state on the exposure of transporter substrates in human

Disease State	Drug	Transporter/Enzyme Substrate	AUC0-last Patients	AUC0-last Healthy Subjects	Mean Ratio	Cmax Patients	Cmax Healthy Subjects	Mean Ratio	Cl/F Patients	CL/F Healthy Subjects	Mean Ratio	Reference
CLD (majority with Child-Pugh grade B or C)	Repaglinide (4 mg P.O.)	OATP1B1, CYP2C8, CYP3A4	368.9 ng*h/mL	91.6 ng*h/mL	4.34	105.4 ng/mL	46.7 ng/mL	2.46	-	-	-	(51)
CLD (Child-Pugh A)	Pitavastatin (2 mg P.O.)	OATP1B1, OATP1B3, BCRP, MRP2, UGT1A3, UGT2B7	174.1 ng*h/mL	135.9 ng*h/mL	1.28	70.7 ng/mL	59.5 ng/mL	1.19	-	-	-	(50)
CLD (Child-Pugh B)	Pitavastatin (2 mg P.O.)	OATP1B1, OATP1B3, BCRP, MRP2, UGT1A3, UGT2B7	481.1 ng*h/mL	135.9 ng*h/mL	3.54	147.1 ng/mL	59.5 ng/mL	2.47	-	-	-	(50)
HD-CKD	Fexofenadine (120 mg P.O.)	P-gp, OATP1B3, OATP2B1	2,327 ng*h/mL	1,008 ng*h/mL	2.3	531.1 ng/mL	246.7 ng/mL	2.2	60 mL/min	135 mL/min	0.44	(109)
CKD (severe, non-dialysis patients)	Pitavastatin (4 mg P.O.)	OATP1B1, OATP1B3, BCRP, MRP2, UGT1A3, UGT2B7	164 ng*h/mL	125.9 ng*h/mL	1.3	74.28 ng/mL	63.12 ng/mL	1.18	-	-	-	(110)
NASH	Morphine-glucuronidesa	MRP3	58.8 μM*min	37.2 μM*min	1.6	343 nM	225 nM	1.5	-	-	-	(60)
NASH	99mTc-mebrofeninb	OATP1B1, OATP1B3, MRP2, MRP3	2,440 µCi*min/L	1,780 µCi*min/L	1.4	286 µCi/L	136 µCi/L	2.1				(56)
Pediatric NASH	Acetaminophen-glucuronidec	MRP3	207.7 nmol*h/mL	143 nmol*h/mL	1.4	-	-	-	-	-	-	(59)

CLD: Chronic Liver Disease; CKD; Chronic Kidney Disease; HD-CKD: hemodialysis-Chronic Kidney Disease; -, no data reported

^aNo significant changes for morphine parent drug were observed

^bAUC_0-180,liver: 277 vs. 433 kcounts*min/sec (liver activity-time curves measured by gamma scintigraphy) in NASH patients vs. healthy subjects (1.6-fold mean ratio)

^cNo significant changes for acetaminophen parent drug were observed