TABLE 1

Compounds that do not obey the Øie-Tozer model together with designated therapeutic activity and literature evidence for interaction with active transporters

Drug	Therapeutic Class	Transporter(s) or Active Mechanism Implicated^{^a}	Reference
Acetylsalicylic acid	NSAID	OAT1	Apiwattanakul et al., 1999
Adefovir	Antiviral	MRP4, OAT1, OAT3, secretory renal CL	Imaoka et al., 2007; Uwai et al., 2007; Varma et al., 2009
Amikacin	Antibacterial	Megalin	Tod et al., 2000; Nagai, 2006
Aminohexanoic acid, 6-	Hematologic agent
Amoxicillin	Antibacterial	PEPT1, PEPT2, OAT1, secretory renal CL	Hill et al., 2002; Li et al., 2006; Varma et al., 2009
Ampicillin	Antibacterial	MRP4, NPT1 (mouse), PEPT1	Yabuuchi et al., 1998; Uchida et al., 2007; Dobson and Kell, 2008
Atracurium	Neuromuscular blocker
Azlocillin	Antibacterial	Secretory renal CL	Varma et al., 2009
Aztreonam	Antibacterial	Secretory renal CL	Varma et al., 2009
Biapenem	Antiinfective
Busulphan	Immunosuppressant/antineoplastic
Carbenicillin	Antibacterial	Secretory renal CL	Varma et al., 2009
Carboplatin	Antineoplastic	ATP7A, ATP7B	Safaei, 2006
Carumonam	Antibacterial
Cefadroxil	Antibacterial	PEPT1, OAT1, OAT3, OAT4, secretory renal CL	Bretschneider et al., 1999; Takeda et al., 2002; Varma et al., 2009
Cefamandole	Antibacterial	OATs, secretory renal CL	Rizwan and Burckhardt, 2007; Varma et al., 2009
Cefatrizine	Antibacterial	Secretory renal CL	Varma et al., 2009
Cefazolin	Antibacterial	OAT1, OAT3, OAT4, MRP4, secretory renal CL	Takeda et al., 2002; Ci et al., 2007; Varma et al., 2009
Cefepime	Antibacterial	OCTN2	Ganapathy et al., 2000
Cefetamet	Antibacterial
Cefixime	Antibacterial	PEPT1, PEPT2, NPT1 (mouse)	Ganapathy et al., 1997; Yabuuchi et al., 1998
Cefmetazole	Antibacterial	MRP4	Uchida et al., 2007
Cefodizime	Antibacterial	Unidentified transporter in isolated rat choroid plexus	Nohjoh et al., 1989
Ceforanide	Antibacterial
Cefotaxime	Antibacterial	OAT1, OAT3, OAT4, secretory renal CL	Takeda et al., 2002; Varma et al., 2009
Cefotetan	Antibacterial
Cefoxitin	Antibacterial
Cefpirome	Antibacterial
Cefprozil	Antibacterial
Ceftazidime	Antibacterial	MRP4	Uchida et al., 2007
Ceftizoxime	Antibacterial	MRP4, NPT1 (mouse)	Yabuuchi et al., 1998; Ci et al., 2007
Ceftobiprole	Antibacterial
Cefuroxime	Antibacterial	Secretory renal CL	Varma et al., 2009
Cephalexin	Antibacterial	MATE1, secretory renal CL	Tanahara et al., 2007; Varma et al., 2009
Cephaloridine	Antibacterial	OAT1, OAT3, OAT4, OCTN2, NPT1 (mouse)	Yabuuchi et al., 1998; Ganapathy et al., 2000; Takeda et al., 2002
Cephalothin	Antibacterial	OAT1, OAT3, OAT4, NPT1 (mouse)	Yabuuchi et al., 1998; Takeda et al., 2002
Cephapirin	Antibacterial
Cephradine	Antibacterial	MATE1, OAT1, NPT1 (mouse)	Yabuuchi et al., 1998; Rizwan and Burckhardt, 2007; Tanihara et al., 2007
Cidofovir	Antiviral	MRP4, OAT1, OAT3, secretory renal CL	Imaoka et al., 2007; Uwai et al., 2007; Varma et al., 2009
Cilastatin	Protease inhibitor	OAT3	Takeda et al., 2001
Cisatracurium	Neuromuscular blocker
Clavulanic Acid	Antibacterial
Dalfopristin	Antibacterial
Dexrazoxane	Immunosuppressant/antineoplastic
Diatrizoic acid (Amidotrizoate)	Contrast agent
Doxacurium	Neuromuscular blocker
Doxifluridine	Immunosuppressant/antineoplastic	CNT1, secretory renal CL	Larráyoz et al., 2004; Varma et al., 2009
Enalaprilat	Antihypertensive	MRP2, secretory renal CL	Liu et al., 2006; Varma et al., 2009
Eptifibatide	Hematologic agent
Ertapenem	Antibacterial
Fluorescein	Contrast agent	OAT3, MRP2, active transport-driven accumulation in mitochondria	Masereeuw et al., 1994; Hawkins et al., 2007
Fluorouracil, 5-	Immunosuppressant/antineoplastic	AQP9, OAT2	Tsukaguchi et al., 1998; Rizwan and Burckhardt, 2007
Foscarnet	Antiviral	MCT1 (rat), NPT1 (mouse)	Yabuuchi et al., 1998; Tamai et al., 1999; Kido et al., 2000
Fosfomycin	Antibacterial
Gadoversetamide	Contrast agent
Gentamicin	Antibacterial	Megalin	Tod et al., 2000; Nagai, 2006
Hydroxyurea	Antineoplastic	OATP2, MDR1	Dogruel et al., 2003
Imipenem	Antibacterial
Iohexol	Contrast agent
Iopamidol	Contrast agent
Iopromide	Contrast agent
Iothalamic acid (iothalamate)	Contrast agent
Isepamicin	Antibacterial	Megalin	Tod et al., 2000; Nagai, 2006
Kanamycin	Antibacterial	Megalin	Tod et al., 2000; Nagai, 2006
Lamifiban	Hematologic agent
Melagatran	Hematologic agent
Meropenem	Antibacterial	OAT1, OAT3, secretory renal CL	Shibayama et al., 2007; Varma et al., 2009
Metocurine	Neuromuscular blocker
Metrizoate	Contrast agent	Secretory renal CL	Varma et al., 2009
Metronidazole	Antiprotozoal/antibacterial
Mezlocillin	Antibacterial	Secretory renal CL	Varma et al., 2009
Miglitol	Hypoglycemic agent
Mivacurium (cis/cis)	Neuromuscular blocker
Moxalactam	Antibacterial
Netilmicin	Antibacterial	Megalin	Tod et al., 2000; Nagai, 2006
Oseltamivir acid	Antiviral	Secretory renal CL, MDR1, PEPT1	Morimoto et al., 2008; Ogihara et al., 2009; Varma et al., 2009
Penicillin G	Antibacterial	MRP4, OATPs, PEPT1, PEPT2, NPT1, OAT1, OAT3, secretory renal CL	Uchino et al., 2000; Varma et al., 2009
Piperacillin	Antibacterial	MRP4, secretory renal CL	Uchida et al., 2007; Varma et al., 2009
Pipecuronium	Neuromuscular blocker
Probenecid	Uricosuric agent/antibacterial adjunct	OAT1, MCT6	Murakami et al., 2005; Rizwan and Burckhardt, 2007
Quinaprilat	Antihypertensive	OAT3, secretory renal CL	Varma et al., 2009; Yuan et al., 2009
Rocuronium	Neuromuscular blocker	OATP1A2	Dobson and Kell, 2008
Streptomycin	Antibacterial
Sulbactam	Antibacterial	MRP4, secretory renal CL	Uchida et al., 2007; Varma et al., 2009
Sulbenicillin	Antibacterial	Secretory renal CL	Varma et al., 2009
Sulfadiazine	Antiprotozoal/antibacterial	Active uptake in leukocytes	Climax et al., 1986
Ticarcillin	Antibacterial	Secretory renal CL	Varma et al., 2009
Tobramycin	Antibacterial	MDR1, megalin	Banerjee et al., 2000; Tod et al., 2000; Nagai, 2006
Tomopenem	Antibacterial
Zanamivir	Antiviral

NSAID, nonsteroidal anti-inflammatory drug; OAT, organic anion transporter; MRP, multidrug resistance protein; CL, clearance; PEPT, peptide transporter; NPT, sodium-phosphate transporter; OCTN, novel organic cation transporter; MATE, multidrug and toxin extrusion protein; CNT, concentrative nucleoside transporter; MCT, monocarboxylic acid transporter.
↵a Compounds classified as exhibiting net secretory renal CL based on threshold defined by Varma et al. (2009) where CLr > 1.2 · f_up · glomerular filtration rate.