TABLE 2

Rat/human and dog/human unbound biliary clearance ratios and assignment of hepatic drug transporter involvement

	Rat/Human CL_bile,u	Dog/Human CL_bile,u	Hepatic Uptake Transporter	Biliary Efflux Transporter	Chemotype
Doxorubicin	1	1	—	MRP2; P-gp^{^a}^,^{^b}^,^{^c}	b
Digoxin	2	1	—	P-gp^{^d}	n
Erythromycin	3	1	—	MRP2; P-gp^{^e}	b
Cefazolin	1685	13	OATP1B1, 1B3^{^f}	BCRP^{^g}	a
Cefamandole	613		^*	MRP2, BCRP^{^h}	a
Cephalexin	90		OATP1B1, 1B3^{^f}	^*	a
Cefotetan	27	4	^*	BCRP^{^g}	a
Cefixime	16		^*	^*	a
Ceftriaxone	14	3	OATP1B3^{^f}^,^{^h}	MRP2^{^g}	a
Cefpiramide	10	1	^*	MRP2, BCRP^{^g}	a
Cefoperazone	10		OATP1B1, 1B3^{^h}^,^ⁱ	MRP2, BCRP^{^g}	a
Valsartan	35		OATP1B1, 1B3^{^j}	MRP2^{^j}	a
Moxalactam	507		^*	^*	a
Methotrexate	11	3	OATP1B1^{^k}	MRP2^{^l}	a
Pravastatin	13		OATP1B1^{^m}	MRP2^ⁿ	a
Diclofenac	11		^*	^*	a
Ranitidine	10		OCT-1^{^o}	P-gp^{^p}	b
Vincristine	162		^*	MRP2; P-gp^{^q}^,^{^r}	b
Methadone	2508		^*	P-gp^{^s}	b
Fexofenadine	11		OATP1B1, 1B3^{^t}^,^{^u}	P-gp^{^u}	z
Ciprofloxacin	73		^*	^*	z
Napsagatran	13	8	^*	^*	z

—, Literature indicates no or inefficient active hepatic uptake; a, b, n, z in the final column indicates acid, base, neutral, and zwitterionic drug.
↵* Indicates that no literature reference was found.
↵^a Fujiwara et al., 2011.
↵^b Hidemura et al., 2003.
↵^c Koike et al., 1997.
↵^d Bi et al., 2006.
↵^e Hariharan et al., 2009.
↵^f Nakakariya et al., 2008a.
↵^g Kato et al., 2008.
↵^h Yamaguchi et al., 2011.
↵ⁱ Nakakariya et al., 2008b.
↵^j Yamashiro et al., 2006.
↵^k Gui et al., 2010.
↵^l Choi et a., 2009.
↵^m Kusuhara and Sugiyama, 2010.
↵ⁿ Watanabe et al., 2009.
↵^o Bourdet et al., 2005.
↵^p Huang et al., 2005.
↵^q van Zanden et al., 2005.
↵^r Watanabe et al., 1995.
↵^s Rodriguez et al., 2004.
↵^t Matsushima et al., 2008.
↵^u Cvetkovic et al., 1999.