TABLE 4

Effects of genetic variability in SLCO1B1 on the pharmacokinetics of drugs

Drug	Dose	n	Ethnicity	Effect	Reference
Atorvastatin	20 mg	32	White	c.521CC vs. 1A/1A: AUC 144%↑, 2-OH-atorvastatin AUC 100%↑	Pasanen et al., 2007
				c.521CC vs. c.521TC: AUC 61%↑
Atorvastatin	20 mg	28	Korean	15/15 vs. 1A/1A, 1A/1B or 1B/1B: AUC 124%↑, 2-OH-atorvastatin AUC↑	Lee et al., 2010
				15/15 vs. 1A/15, 1B/15: AUC 84%↑
Atrasentan	10 mg	44 (single dose)	Mixed	Poor vs. extensive activity genotype^{^a}: single dose AUC 73%↑	Katz et al., 2006
		38 (steady state)		Intermediate vs. extensive activity genotype: single dose AUC 14%↑, steady-state AUC 27%↑ (no poor activity genotypes in steady state)
Cyclosporine	3 mg/kg i.v. and 10 mg/kg p.o.	104 renal transplant recipient children	White	c.521T>C: N.S.	Fanta et al., 2008
Ezetimibe	20 mg	35	White	1B/1B vs. 1A/1A: 51%↓	Oswald et al., 2008
				1A/1B vs. 1A/1A: 21%↓
Fexofenadine	180 mg	20	White	c.521CC vs. c.521TT: AUC 127%↑	Niemi et al., 2005d
				c.521CC vs. c.521TC: AUC 76%↑
Fluvastatin	40 mg	32	White	c.521T>C: N.S.	Niemi et al., 2006b
Irinotecan	100 mg/m² or 375 mg/m²	71 cancer patients	Asian	15/15 or 1B/15 vs. 1A/1B or 1B/1B: CL 52%↓, SN-38G C_max 65%↓, AUC 45%↓	Xiang et al., 2006
				15/15 or 1B/15 vs. 1A/1A: C_max 83%↑, AUC 127%↑, CL 67%↓, SN-38 C_max 130%↑, AUC 86%↑, SN-38G C_max 81%↓, AUC 70%↓
Irinotecan	80 mg/m²	81 cancer patients	Korean	g.−11187AA vs. g.−11187GA or g.−11187GG: SN-38 AUC 113%↑	Han et al., 2008
	and cisplatin 60 mg/m²			c.521CC or c.521TC vs. c.521TT: SN-38 AUC 29%↑
Irinotecan	80 or 65 mg/m²	107 cancer patients	Korean	c.521CC or c.521TC vs. c.521TT: SN-38 AUC 26%↑	Han et al., 2009
Irinotecan	300 or 350 mg/m²	85 cancer patients		c.521CC or c.521TC vs. c.521TT: irinotecan AUC 19%↑	Innocenti et al., 2009
Irinotecan	100, 150, or 60 mg/m² with 60 mg/m² cisplatin; 70 mg/m² with 80 mg/m² cisplatin	117 cancer patients	Japanese	c.521CC or c.521TC vs. c.521TT: SN-38 AUC↑	Sai et al., 2010
Lopinavir	variable, with 200 mg of ritonavir	148 HIV patients	White	c.521CC vs. c.521TT: CL 21%↓	Lubomirov et al., 2010
				c.521TC vs. c.521TT: CL 14%↓
				rs4149032 homozygotes vs. noncarriers: CL 29%↑
				rs4149032 homozygotes vs. heterozygotes: CL 21%↑
				c.463AA vs. c.463CC: CL 116%↑
				c.463AA vs. c.463CA: CL 104%↑
Lopinavir	variable, with ritonavir	99 HIV patients	Mixed	c.521CC vs. c.521TT: C_trough 49%↑	Kohlrausch et al., 2010
				c.521CC vs. c.521TC: C_trough 16%↑
Lopinavir	400 mg, with 100 mg of ritonavir b.i.d.	349 HIV patients	Unknown	c.521CC vs. c.521TT: C_min and C_2–6↑	Hartkoorn et al., 2010
				c.521CC vs. c.521TC: C_min and C_2–6↑
				c.521TC vs. c.521TT: C_min and C_2–6↑
Methotrexate	2–5 g/m²	434 + 206 children with ALL	Mixed	rs4149081/rs11045879: 6–14 ml/min/m²↑ CL per variant allele	Treviño et al., 2009
				c.521T>C: 4–14 ml/min/m²↓ CL per C-allele
Mycophenolic acid	0.75–1 g b.i.d. with tacrolimus	87 renal transplant recipients	Japanese	c.388A>G or c.521T>C: N.S.	Miura et al., 2007
Mycophenolic acid	0.5–1 g b.i.d. with tacrolimus	80 renal transplant recipients	Japanese	c.521TC or c.521CC vs. c.521TT: mycophenolic acid glucuronide AUC 27%↓	Miura et al., 2008
Nateglinide	90 mg	17	Chinese	c.521CC vs. c.521TT: AUC 108%↑	Zhang et al., 2006
				c.521TC vs. c.521TT: AUC 82%↑
Nateglinide	60 mg	24	White	1B/1B vs. 1A/1A: N.S.	Kalliokoski et al., 2008b
Nateglinide	60 mg	32	White	c.521CC or c.521TC vs. 1A/1A: N.S.	Kalliokoski et al., 2008c
Olmesartan	10 mg	10	Japanese	15/15 vs. 1B/1B: CL_oral↓	Suwannakul et al., 2008
Pioglitazone	15 mg	32	White	c.521T>C: N.S.	Kalliokoski et al., 2008e
Pitavastatin	1–8 mg	24	Korean	c.521TC vs. 1B/1B: dose-normalized AUC 76%↑, C_max 123%↑, t_1/2 30%↑	Chung et al., 2005
				c.521TC vs. 1A/1B or 1B/1B: dose-normalized AUC 25%↑, C_max 62%↑
Pitavastatin	2 mg	38	Japanese	c.521TC vs. 1B/1B: AUC 76%↑	Ieiri et al., 2007
				15/15 vs. 1B/1B: AUC 208%↑
				15/15 vs. 1B/15: AUC 74%↑
Pitavastatin	4 mg	11	Korean	15/15 vs. 1A/1A: AUC 162%↑	Deng et al., 2008b
Pitavastatin	2 mg	15	Chinese	c.388GG or c.388AG vs. c.388AA: AUC 46%↓, C_max 42%↓	Wen and Xiong, 2010
Pravastatin	10 mg	23	Japanese	1B/15 vs. 1B/1B: CL_nr 45%↓	Nishizato et al., 2003
Pravastatin	40 mg	30	White	c.521TC vs. 1A/1A: AUC 42%↑	Mwinyi et al., 2004
				c.521TC vs. 1A/1B or 1B/1B: AUC 118%↑
Pravastatin	40 mg	41	White	g.−11187GA vs. g.−11187GG: AUC 98%↑	Niemi et al., 2004
				c.521TC vs. c.521TT: AUC 106%↑
				*15 heterozygotes vs. non-carriers: AUC 93%↑
				g.−11187A-c.388G-c.521C heterozygotes vs. non-carriers: AUC 130%↑
Pravastatin	40 mg/day	16	White	g.−11187G-c.388G-c.521C or g.−11187A-c.388G-c.521C carriers vs. non-carriers: steady-state AUC 110%↑	Igel et al., 2006
Pravastatin	10 mg	23	Japanese	1B/1B vs. 1A/1A: AUC 35%↓	Maeda et al., 2006a
				1B/15 vs. 1A/15: AUC 45%↓
Pravastatin	40 mg	32	White	c.521CC vs. 1A/1A: AUC 91%↑, male 232%↑	Niemi et al., 2006b
				c.521CC vs. c.521 TC: AUC 74%↑, male 102%↑
Pravastatin	40 mg	107	Mixed	1A/15 vs. 1A/1A: AUC 45%↑	Ho et al., 2007
				1A/15 vs. 1B/1B: AUC 80%↑
				15/15 vs. 1A/1A: AUC 92%↑
				15/15 vs. 1B/1B: AUC 149%↑
Pravastatin	40 mg	11	Korean	15/15 vs. 1A/1A: AUC 99%↑	Deng et al., 2008b
Repaglinide	0.25 mg	56	White	c.521CC vs. c.521TT: AUC 188%↑	Niemi et al., 2005b
				c.521CC vs. c.521TC: AUC 107%↑
Repaglinide	0.5 mg	32	White	c.521CC vs. 1A/1A: AUC 72%↑, M2 AUC 112%↑, M4 AUC 81%↑	Kalliokoski et al., 2008c
Repaglinide	0.5 mg	24	White	1B/1B vs. 1A/1A: AUC 32%↓	Kalliokoski et al., 2008b
Repaglinide	0.25 mg	20	White	c.521CC vs. 1A/1A: AUC 82%↑	Kalliokoski et al., 2008d
	0.5 mg			c.521CC vs. 1A/1A: AUC 72%↑
	1 mg			c.521CC vs. 1A/1A: AUC 56%↑
	2 mg			c.521CC vs. 1A/1A: AUC 108%↑
Rifampin	450 or 600 mg	72 patients with pulmonary tuberculosis + 16 healthy volunteers	Mixed	c.463CA vs. c.463CC: AUC 42%↓	Weiner et al., 2010
Rosiglitazone	4 mg	32	White	c.521T>C: N.S.	Kalliokoski et al., 2008e
Rosuvastatin	40 mg	36	White	15/15 vs. 1A/1A: AUC 117%↑	Lee et al., 2005
				15/15 vs. 1A/1B: AUC 108%↑
		36	Chinese	N.S. (no c.521CC included)
		35	Malay	N.S. (no c.521CC included)
		35	Asian-Indian	N.S. (no c.521CC included)
Rosuvastatin	10 mg	32	White	c.521CC vs. 1A/1A: AUC 65%↑	Pasanen et al., 2007
Rosuvastatin	10 mg	30	Korean	15/15 vs. 1A/1A: AUC 119%↑	Choi et al., 2008
				1A/15 vs. 1A/1A: AUC 91%↑
				15/15 vs. 1A/15: AUC 82%↑
Simvastatin	40 mg	32	White	c.521CC vs. 1A/1A: simvastatin acid AUC 221%↑	Pasanen et al., 2006b
				c.521CC vs. c.521TC: simvastatin acid AUC 162%↑
Temocapril	2 mg	23	Japanese	N.S.	Maeda et al., 2006a
Torsemide	10 mg	99	White	1B/1B vs. 1A/1A: CL_nr 40%↑	Vormfelde et al., 2008
				5/5 vs. 1A/1A: CL_nr 68%↓
				15/15 vs. 1A/1A: CL_nr 35%↓
Torsemide	10 mg/day	24	White	c.521TC vs. c.521TT: AUC 38%↑	Werner et al., 2008
Torsemide	10–20 mg/day	90 patients	White	c.521CC or c.521TC vs. c.521TT: AUC↑	Werner et al., 2010
Valsartan	40 mg	23	Japanese	N.S.	Maeda et al., 2006a

*1A, c.388A-c.521T; *1B, c.388G-c.521T; *5, c.388A-c.521C; *15, c.388G-c.521C; ALL, acute lymphoblastic leukemia; AUC, area under the plasma concentration-time curve; CL, clearance; CL_nr, non-renal clearance.
↵a |Extensive activity genotype is defined as homozygosity for high-activity haplotype (c.521T-c.1463G), intermediate activity as heterozygosity for low-activity haplotype (c.521C-c.1463G, c.521T-c.1463C, c.521C-c.1463C), and poor activity as homozygosity or compound heterozygosity for low-activity haplotype.