TABLE 4

Drugs, prodrugs, and drug metabolites that are transported by human organic cation transporters

Drug metabolites are indicated in italics. Charge of major microspecies at pH 7.4 was calculated with program MarvinSketch of ChemAxon. Acyclovir: Takeda et al., 2002; Tanihara et al., 2007, albuterol: Hendrickx et al., 2013, amantadine: Busch et al., 1998; Bednarczyk et al., 2003; Amphoux et al., 2006; Tsuda et al., 2009b; Astorga et al., 2012; Sandoval et al., 2018, amiloride: Biermann et al., 2006; Ahlin et al., 2008; Choi et al., 2011; Astorga et al., 2012; Hendrickx et al., 2013, amiodarone: Hendrickx et al., 2013, amisulpride: dos Santos Pereira et al., 2014, D-amphetamine: Amphoux et al., 2006; Zhu et al., 2010; Wagner et al., 2017, apomorphine: Ahlin et al., 2008; Hendrickx et al., 2013, atecegatran: Matsson et al., 2013, atenolol: Hendrickx et al., 2013, atropine: Müller et al., 2005; Ahlin et al., 2008; Astorga et al., 2012; Chen et al., 2017b; Sandoval et al., 2018, benzamil: Hendrickx et al., 2013; berberine, Nies et al., 2008; Sun et al., 2014, buformin: Futatsugi et al., 2016, bupropion: Sandoval et al., 2018, butylscopolamine: Chen et al., 2017b, camostat: Hendrickx et al., 2013; Wittwer et al., 2013, captopril: Masuda et al., 2006, CDPCP: Lovejoy et al., 2008, cephradine: Tanihara et al., 2007, cephalexin: Tanihara et al., 2007, chloroquine: Zolk et al., 2009a; Müller et al., 2011; Belzer et al., 2013; Hubeny et al., 2016; Chen et al., 2017b, chlorprothixene: Hendrickx et al., 2013, cimetidine: Zhang et al., 1998; Ohashi et al., 1999; Ciarimboli et al., 2004; Peltekova et al., 2004; Suhre et al., 2005; Tahara et al., 2005; Masuda et al., 2006; Tanihara et al., 2007; Lee et al., 2009; Ohta et al., 2009; Tsuda et al., 2009b; Kido et al., 2011; Belzer et al., 2013; Hendrickx et al., 2013; Sprowl et al., 2013; Thévenod et al., 2013; Lechner et al., 2016; Martínez-Guerrero et al., 2016; Yin et al., 2016; Müller et al., 2018; Sandoval et al., 2018, cisplatin: Ciarimboli et al., 2005b; Yonezawa et al., 2006; Filipski et al., 2008; Sprowl et al., 2013, clidinium: Hendrickx et al., 2013, clofarabine: Drenberg et al., 2017, cobicistat: Lepist et al., 2014; Kikuchi et al., 2019, colistin: Visentin et al., 2017a, cycloguanil: van der Velden et al., 2017; Matthaei et al., 2019, cytarabine: Drenberg et al., 2017, diltiazem: Ahlin et al., 2008; Umehara et al., 2008; Tsuda et al., 2009b; Grube et al., 2011; Hendrickx et al., 2013, diphenylhydramine: Müller et al., 2005; Tsuda et al., 2009b; Zolk et al., 2009a; Belzer et al., 2013; Boxberger et al., 2014, 2018, disopyramide: Zhang et al., 1998; Hasannejad et al., 2004; Ahlin et al., 2008; Tsuda et al., 2009b; Zolk et al., 2009b; Kido et al., 2011; Belzer et al., 2013; Hendrickx et al., 2013, emtricitabine: Minuesa et al., 2009; Reznicek et al., 2017; Zeng et al., 2019, entecavir: Yang et al., 2016; Ma et al., 2017, ethambutol: Parvez et al., 2018, etilefrine: Müller et al., 2005, etoposide: Hu et al., 2012, famotidine: Bourdet et al., 2005; Sata et al., 2005; Tahara et al., 2005; Tsuda et al., 2009b; Astorga et al., 2012; Wittwer et al., 2013; Lechner et al., 2016; Martínez-Guerrero et al., 2016, fampridine: Xiao et al., 2018, fenoterol: Hendrickx et al., 2013; Tzvetkov et al., 2018, fexofenadine: Matsushima et al., 2009, fludarabine: Drenberg et al., 2017, fluorouracil: Drenberg et al., 2017, fluoxetine: Tzvetkov et al., 2013; Boxberger et al., 2014, 2018; Sandoval et al., 2018; Zhu et al., 2018, formoterol: Hendrickx et al., 2013; Tzvetkov et al., 2018, furamidine, Ming et al., 2009, gabapentin: Urban et al., 2008; Futatsugi et al., 2016, ganciclovir: Takeda et al., 2002; Tanihara et al., 2007, gentamicin: Gai et al., 2016, gemcitabine: Drenberg et al., 2017, glycopyrrolate: Hendrickx et al., 2013, ifosfamid: Ciarimboli et al., 2011, homatropine: Chen et al., 2017b, imatinib: Tanihara et al., 2009; Kido et al., 2011; Minematsu and Giacomini, 2011; Schmidt-Lauber et al., 2012; Wittwer et al., 2013; Boxberger et al., 2014; Nies et al., 2014; Blanc Mettral et al., 2019, indacaterol: Hendrickx et al., 2013; ipratropium: Zolk et al., 2009b; Nakamura et al., 2010a; Kido et al., 2011; Belzer et al., 2013; Hendrickx et al., 2013; Chen et al., 2017b, ketamine: Hendrickx et al., 2013; Keiser et al., 2018, lamivudine: Jung et al., 2008; Minuesa et al., 2009; Chen et al., 2017b, lappaconitine: Hendrickx et al., 2013, levofloxacin: Okuda et al., 2006; Tanihara et al., 2007, lidocaine: Hasannejad et al., 2004; Peltekova et al., 2004; Umehara et al., 2008, memantine: Busch et al., 1998; Amphoux et al., 2006; Ahlin et al., 2008; Hendrickx et al., 2013, mepenzolate: Hendrickx et al., 2013, metformin: Bourdet et al., 2005; Kimura et al., 2005, 2009; Masuda et al., 2006; Tanihara et al., 2007; Chen et al., 2009b, 2010a, 2017b; Nies et al., 2009; Zolk et al., 2009a; Meyer zu Schwabedissen et al., 2010; Astorga et al., 2012; Belzer et al., 2013; Hendrickx et al., 2013; Nakamichi et al., 2013; Futatsugi et al., 2016; Lechner et al., 2016; Martínez-Guerrero et al., 2016; Sandoval et al., 2018, metamphetamine: Wagner et al., 2017, metoclopramide: Ahlin et al., 2008; Hendrickx et al., 2013; Matthaei et al., 2016, mildronate: Grube et al., 2006; Grigat et al., 2009, nadolol: Misaka et al., 2016, naratriptan: Matthaei et al., 2016, nitidine: Li et al., 2014, nizatidine: Hendrickx et al., 2013, morphine: Ahlin et al., 2008; Tzvetkov et al., 2013; Zhu et al., 2018, oxophenonium: Hendrickx et al., 2013, oxaliplatin: Yonezawa et al., 2006; Yokoo et al., 2007, 2008; Jong et al., 2011; Sprowl et al., 2013, oxytrospium: Wenge et al., 2011, pentamidine: Jung et al., 2008; Ming et al., 2009; Kido et al., 2011; Wittwer et al., 2013, perphenazine: Hendrickx et al., 2013, phenamil: Hendrickx et al., 2013, phenformin: Dresser et al., 2002; Suhre et al., 2005; Astorga et al., 2012; Hendrickx et al., 2013; Futatsugi et al., 2016, picoplatin: More et al., 2010, pindolol: Bednarczyk et al., 2003; Umehara et al., 2008; Hendrickx et al., 2013, pirbuterol: Tzvetkov et al., 2018, pivaloylcarnitine: Ohnishi et al., 2008, pramipexole: Knop et al., 2015, prazosin: Hayer-Zillgen et al., 2002; Ahlin et al., 2008, 2011; Minematsu et al., 2010; Hendrickx et al., 2013; Wittwer et al., 2013; Moss et al., 2015, procaterol: Hendrickx et al., 2013, procainamide: Gorboulev et al., 1997; Zhang et al., 1998; Wu et al., 2000; Bednarczyk et al., 2003; Hasannejad et al., 2004; Masuda et al., 2006; Tanihara et al., 2007; Umehara et al., 2008; Astorga et al., 2012; Hendrickx et al., 2013, proguanil: Astorga et al., 2012; van der Velden et al., 2017; Matthaei et al., 2019, propranolol: Dudley et al., 2000; Urakami et al., 2004; Ahlin et al., 2008; Santini et al., 2008; Umehara et al., 2008; Zolk et al., 2009a,b; Grube et al., 2011; Astorga et al., 2012; Belzer et al., 2013; Hendrickx et al., 2013; Matthaei et al., 2016, prothionamide: Parvez et al., 2018, pyrilamine: Ohashi et al., 1999, 2002; Yabuuchi et al., 1999; Grigat et al., 2007, quinine: Gorboulev et al., 1997; Müller et al., 2005; Masuda et al., 2006; Tanihara et al., 2007; Ahlin et al., 2008; Grigat et al., 2009; Astorga et al., 2012; Tzvetkov et al., 2012; Hubeny et al., 2016; van der Velden et al., 2017, quinidine: Ohashi et al., 1999, 2002; Bednarczyk et al., 2003; Hasannejad et al., 2004; Peltekova et al., 2004; Bourdet et al., 2005; Masuda et al., 2006; Grigat et al., 2007, 2009; Ahlin et al., 2008, 2011; Umehara et al., 2008; Tsuda et al., 2009b; Zolk et al., 2009a; Minematsu et al., 2010; Astorga et al., 2012; Belzer et al., 2013; Hendrickx et al., 2013; Lechner et al., 2016; Sandoval et al., 2018, ranitidine: Bednarczyk et al., 2003; Bourdet et al., 2005; Müller et al., 2005; Tahara et al., 2005; Tsuda et al., 2009b; Meyer zu Schwabedissen et al., 2010; Astorga et al., 2012; Hendrickx et al., 2013; Martínez-Guerrero et al., 2016, relebactam: Chan et al., 2019, ribavirin: Drenberg et al., 2017, rizatriptan: Matthaei et al., 2016, salbumatol: Salomon et al., 2015; Tzvetkov et al., 2018, saracatinib: Harrach et al., 2017, selegiline: Hendrickx et al., 2013, sulpiride: dos Santos Pereira et al., 2014; Bai et al., 2017a; Li et al., 2017; Takano et al., 2017, sumatriptan: Hendrickx et al., 2013; Matthaei et al., 2016, terazosine: Ahlin et al., 2008; Hendrickx et al., 2013, terbutaline: Hendrickx et al., 2013; Tzvetkov et al., 2018, tetracycline: Tanihara et al., 2007, tiotropium: Nakamura et al., 2010a; Hendrickx et al., 2013, triamterene: Hendrickx et al., 2013, tropisetron: Tzvetkov et al., 2012, 2013, topotecan: Tanihara et al., 2007; Wittwer et al., 2013; Lechner et al., 2016, trimethoprim: Urakami et al., 2004; Sata et al., 2005; Ahlin et al., 2008; Jung et al., 2008; Belzer et al., 2013; Hendrickx et al., 2013; Lepist et al., 2014; Lechner et al., 2016; Martínez-Guerrero et al., 2016; Chen et al., 2017a; Sandoval et al., 2018; Kito et al., 2019, trospium: Choi et al., 2011; Wenge et al., 2011; Bexten et al., 2015; Hacker et al., 2015; Chen et al., 2017b, valproylcarnitine: Ohnishi et al., 2008, varenicline: Feng et al., 2008; Hendrickx et al., 2013, verapamil: Zhang et al., 1998; Yabuuchi et al., 1999; Wagner et al., 2000; Ohashi et al., 2002; Peltekova et al., 2004; Grube et al., 2006, 2011; Grigat et al., 2007, 2009; Ahlin et al., 2008, 2011; Tsuda et al., 2009b; Zolk et al., 2009b; Minematsu et al., 2010; Astorga et al., 2012; Belzer et al., 2013; Hendrickx et al., 2013; Tzvetkov et al., 2013; Boxberger et al., 2014; Jouan et al., 2014; Bexten et al., 2015; Parvez et al., 2018; Sandoval et al., 2018; Zhu et al., 2018, xamoterol: Hendrickx et al., 2013, zolmitriptan: Matthaei et al., 2016.

Drug (Charge of Major Microspecies at pH 7.4) Medical ApplicationApparent Km (IC50) [µM]
hOCT1hOCT2hOCT3hOCTN1hOCTN2hMATE1hMATE2-K
Acyclovir (0) antiviral1512640a4320a
Albuterol (+) antiasthmatictt
Amantadine (+) antiviral(10, 236)10–51 (23)(>1000)(7.5,a 112a)(89,a 1170a)
Amiloride (+) diuretict (57)95 (23)(2.4a)t (3.1a)
Amiodarone (+) antiarrhythmicn.t.d. (21)t
Amisulpride (+) antischizophrenic31168192180185
D-Amphetamine (+) stimulantn.t.d. (97, 202)0.8, 534 (0.7–145)n.t.d. (24–460)14a (94a)16a (158a)
Apomophine (+) anti-Parkinsonn.t.d.t
Atecegatran, (+), anticoagulanttt
Atenolol (+) antihypertensivett
Atropine (+) mydriatic5.9 (1.2–12)4.4 (1.3–38)48 (42, 446)(5.9a)(53a)n.t.d. (5.9,a 18a)n.t.d. (53,a 69a)
Benzamil (+) diuretictt
Berberin (+) antidepressant151.0, 4.4 (0.4–0.9)2.2 (0.4–10)
Buformin (+) antidiabetict
Bupropion (+) antidepressantn.t.d.t (8.6–32)
Butylscopolamine (+) spasmolytic23 (28)16 (1820)110 (2572)29a (8.2a)n.t.d. (38a)
Camostat (+) antineoplastic,tn.t.d. (17)(2.9a)(13a)
Captopril (−) antihypertensivet
cDPCP (+) antineoplastictt
Cephradine (+−) antibiotictn.t.d.
Cephalexin (+) antibiotictn.t.d.
Cephaloridine (+) antibiotic(<1000)t (790)
Chloroquine (++) antimalarial(13, 1097)(8.9–1096)t (1.5a)(4.0a)
Chlorprothixene (+) antipsychioticn.t.d.t
Cimetidine (0) antacid60 (95–2830)15, 73 (1–560)(88, 240)(435)(<1000)2.2,a 170a (1.1a–37,a 6.7)120,a 370a (5.5a–47,a 39)
Clidinium (+) anti ulcert
Cisplatin (++−) antineoplastict11 (1.5)n.t.d.n.t.d.n.t.d.tt
Clofarabine (0) antineoplastict
Cobicistat (0) antiviralt (24)(>100)(1.9,a 4.4a)(3.2,a 36a)
Colistin (++++) antibioticn.t.d.n.t.d.t (22.7, 2500)
Cycloguanil (+), antimalarialt (18)tttt
Cytarabine (0) antineoplasticn.t.d.n.t.d.n.t.d.2.0n.t.d.
O-desmethyltramadol (+) analgetic149 (172)
Diltiazem (+) antihypertensivet (1.7–16)n.t.d., (>1000)(50)(126)(13a)(117a)
Diphenylhydramine (+) antiemetict (3.4, 4.1)(5.8–21)(87a)(267a)
Disopyramide (+) antiarrhythmict (15, 82)n.t.d., (2.9–324)t (457)(84,a 66)(292a)
Emtricitabine (0) antiviral(0.00002)(0.002)n.t.d. (0.0005)490, 13,300n.t.d.tn.t.d.
Entecavir (0) antiviral300t24001900200,a 1600a200,a 900a
Etoposide (0) antineoplastic150 (55)
Ethambutol (+) antibiotic526212337455
Etilefrine (+) hypertensive(447)(4009)2800 (4450)
Famotidine (0) antacidt (28, >300)56 (36, 114)(6.7, 11)(0.3a–6.7a)(3.1a–36a)
Fampridine (+) treatment of MS51 (67)n.t.d., n.i.d.n.t.d., n i.d.
Fenoterol (+) antiasthmatic1.8t20
Fexofenadine (+−) antiallergictn.t.d.
Fludarabine (−) antineoplastict
Fluorouracil (−) antineoplastict
Formoterol (+) antiasthmatictn.t.d.
Fluoxetine (+) antidepressantt (6.0–9.1)(3.3–57)
Furamidine (+) antiparasitic6.1 (7.4)t (182)n.d.t. (20)
Gabapentin (+−) antiepileptic417
Ganciclovir (0) antiviral5165120a4280a
Gentamicin (+++++) antibiotict
Gemcitabine (0) antineoplastict (38,000)
Glycopyrrolate (+) antisecretorytt
Homatropine (+) mydriaticn.t.d. (4.0)1.3 (45)140 (13)n.t.d. (19a)n.t.d. (128a)
Ifosfamid (0) antineoplastict (624)
Imatinib (+) antineoplasticn.t.d. (0.1–107)n.t.d. (<1–6.7)n.t.d. (4.4, 26)t (31)n.t.d.t (0.02a–0.35a)(0.5a–2.9a)
Indacaterol (+) brochodilatatortn.t.d.
Ipratropium (+) bronchodilatator9, 14 (0.2–17)0.3 (0.17–15)1.7 (2.5)444 (>1000)53 (>1000)45a (31a)96a (63a)
Ketamine (+) analgetic74a34a53,a 365n.t.d.n.t.d.
Lamivudine (0) antiviral249, 1250 (1 × 10−5, 1900)249, 1900 (8 × 10−6, 3450)2140 (2 × 10−5, 2400)(>1000a)(1510a)
Lappaconitine (+) analgesicn.t.d.t
Levofloxacin (−) antibiotic(127)t
Lidocaine (+) antiarrhythmic(294)139 (656)(0.8)
Mepenzolate (+) anti GI ulcerst
Metamphetamine (+) stimulantn.t.d. (0.3, 400)2.1 (1.2, 58)n.t.d. (300)21a (107a)18a (84a)
Metformin (++), antidiabetic1470, 2160 (1230, 9480)285–3170 (521–2370)1090, 2260 (2330)t227a–780,a (47a–667a)1050,a 1980a (89a–6516a)
Metoclopramide (+) antiemetict (16, 95)t
Memantine (+) anti-Parkinsonn.t.d. (4, 27)34 (7.3)(236)
Mildronate (+−) cardioprotective26 (21)
Morphine (+) pain relieving3.4 (4.2, 28)tn.t.d. (538)n.t.d.
Nadolol (+), antihypertensivet122531a372a
Naratriptan (+) antimigrainet (25)
Nitidine (+) antimalarialttt
Oxaliplatin (++−) antineoplastict>1000tt (950)t (8900)tt
Oxophenonium (+) antiulcertt
Oxibutynin (+) antioveractive bladder8.8 (20)t (128)t (130)
Pentamidine (++) antiparasitic36 (16, 22)t (1.2–11)n.t.d, (<1–15)(2.0, 2.7a)10 (10a)
Perphenazine (+) antidepressanttn.t.d.
Phenamil (0) stimulantn.t.d.t
Phenformin (+) antidiabetict (10)t (15, 65)t(6.1a)(11a)
Pirbuterol (+) antiasthmatict
Picoplatin (+++−) antineoplasticttt
Pindolol (+) antihypertensiven.t.d., (10, 39)t(>1000)
Pivaloylcarnitine (+−) anti-inflammatory166 (308)
Prazosin (+) antihypertensiven.t.d. (1.6–51)t (14, 80)(14)(1.6a)
Pramipexole (+) anti-Parkinsontt
Procaterol (+) antiasthmatictt
Procainamide (+) antiarrhythmict (15, 74)t (28, 406)t (355, 738)1230,a (24,a 217a)1580,a 4100a (19,a 178a)
Proguanil (+) prodrug, antimalarial8.1, 189.1tt (4.4a)n.t.d. (1.4a)
Propanolol (+) antiarrhythmicn.t.d. (1.3–113)12 (67–229)(78, 113)(7.8a)(7.7a)
Prothionamide (0) antituberculosis806
Pyrilamine (+) antiallergict (182)t (<500)
Quinine (+) antimalarialn.t.d. (3.5–96)n.t.d. (3.4–23)(37)t (1.9a)t (6.4a)
Quinidine (+) antiarrhythmicn.t.d. (5–340)n.t.d. (6.4–91)216 (18)t (68)t (<500)(1.6a –>100a)n.t.d, (1.5a–29a)
Ranitidine (++) antacid63, 70 (22–33)65 (76)n.t.d. (290, 372)(5.4a–25,a 18, 19)(10,a 25a)
Relebactam (+−) in combination with β-lactam antibioticstt
Ribavirin (0) antiviralt
Rizatriptan (+) antimigrainet (41)
Salbumatol (+) antiasthmatict
Saracatinib (+) antirheumatict (57)t (0.9)t (50)42 (0.072)n.t.d.n.d.t.
Selegiline (+) anti-Parkinsonn.t.d.t
Sumatriptan (+) antimigraine55 (47)t
Sulpiride (+) antidepressant2.6, 260 (182)26–18716025023515,a 4026,a 60
Terazosine (+) treatment of micturition disturbancet (24)t
Terbutaline (+) antiasthmatictt
Tetracycline (−) antibiotict
Trimethoprim (+) antibiotict (20–57)t (14–1318)(12)2.3 (2.7a–>100a)0.018 (0.42a–1.9a)
Tiotropium (+) bronchodilatatortttt
Topotecan (+) antineoplastic(61)70a (1.3a–27a)60a (5.4a–16,a 8.6)
Triamterene (0) diuretictt
Tropisetron (+) antiemetict (3.3, 8.5)
Trospium (+) treatment of overactive bladder15–106 (5.3–18)0.6, 8.0 (0.07–7.3)4.4 (12–1000)(>100)15a (12a)8.2a (5.1a)
Valproylcarnitine (+−) anti-inflammatory168 (458)
Varenicline (+) antismoke addictiont370
Verapamil (+) antiarrhythmicn.t.d. (1–33)n.t.d. (0.6–92)(57)t (8–25)t (21, 51)(28,a 42a)t (32,a 38a)
Xamoterol (+) cardiac stimulanttt
Zolmitriptan (+) antimigrainet (>1000)
  • n.t.d., no transport detected under the employed experimental conditions; t, transported.

  • a Uptake measurements performed in presence of an outwardly directed proton gradient; IC50 values are presented in brackets.