Inhibition in vitro results of digoxin MDR1-mediated efflux: IC50s based on ER, PappAB, or PappBA, ordered from the lowest IC50(ER) to the highest
| Therapeutic Indication | Compound Name | IC50(ER) | S.D. | IC50(PappAB) | S.D. | IC50(PappBA) | S.D. |
|---|---|---|---|---|---|---|---|
| (µM) | (µM) | (µM) | |||||
| MDR-modulating agent | Zosuquidar | 0.019 | 0.001 | 0.07 | 0.025 | 0.051 | 0.007 |
| MDR-modulating agent | Elacridar | 0.025 | 0.001 | 0.09 | 0.01 | 0.052 | 0.005 |
| MDR-modulating agent | Valspodar | 0.38 | 0.06 | 0.99 | 0.09 | 0.48 | 0.19 |
| Antiarrhythmics | Dronedarone | 0.7 | 0.1 | 10.1 | 4.6 | 7.5 | 4.3 |
| Immunosuppressant | Cyclosporin A | 1.1 | 0.2 | 3.7 | 0.4 | 3.02 | 0.23 |
| Antifungal | Ketoconazole | 1.2 | 0.3 | >10 | n.c. | >10 | n.c. |
| β-Blocker | Carvedilol | 1.3 | 0.4 | 12.8 | 3.9 | 15.1 | 3.8 |
| Antifungal | Itraconazole | 1.8 | 0.4 | 11.0 | 3 | 6.3 | 2.1 |
| Antihypertensive | Mibefradil | 1.9 | 0.2 | 8.4 | 2.6 | 10.5 | 2.0 |
| Antihypertensive | Verapamil | 2.8 | 0.5 | 11.6 | 3.4 | 11.3 | 4.3 |
| Antihypertensive | Nicardipine | 3.8 | 1 | >100 | n.c. | >100 | n.c. |
| Antihypertensive | Felodipine | 4.2 | 0.4 | 17.1 | 4.0 | 13.3 | 1.7 |
| Antianginal | Diltiazem | 4.6 | 0.2 | 32.0 | 10.3 | >100 | n.c. |
| Antiarrhythmic | Quinidine | 4.9 | 0.9 | 29.1 | 3.7 | 17.8 | 4.5 |
| Antihypertensive | Isradipine | 7.7 | 1.8 | >30 | n.c. | >30 | n.c. |
| Antiarrhythmics | Amiodarone | 9.6 | 1.1 | >20 | n.c. | >20 | n.c. |
| Antihypertensive | Telmisartan | 12.2 | 3.7 | 43.0 | 10.8 | 40.7 | 9.7 |
| Antidepressant | Sertraline | 12.9 | 2.3 | 23.2 | 9.3 | >30 | n.c. |
| Antianginal | Ranolazine | 14.1 | 2.2 | 86.6 | 13.9 | 28.9 | 17.4 |
| Antidiabetic | Troglitazone | 15.9 | 0.7 | 36.0 | 11.4 | >30 | n.c. |
| Antiviral | Etravirine | 16.4 | 3.3 | 86.5 | 57.7 | 165 | 85 |
| Diuretic | Conivaptan | 16.6 | 5.9 | 23.4 | 12.1 | 12.6 | 6.5 |
| Antihypertensive | Nitrendipine | 18.2 | 3.7 | >30 | n.c. | >30 | n.c. |
| Antiarrhythmics | Propafenone | 20.3 | 1.5 | 60.1 | 20.0 | 45.4 | 8.6 |
| Antiviral | Ritonavir | 21.3 | 1.3 | 48.5 | 5.3 | 60.5 | 14.1 |
| Vasodilator | Dipyridamole | 21.5 | 3.7 | 45.8 | 8.1 | 28.5 | 5.7 |
| Hyponatremia | Tolvaptan | 25.9 | 4.3 | >300 | n.c. | 98.7 | 49.3 |
| Antibiotic | Clarithromycin | 39.7 | 11.3 | >100 | n.c. | >100 | n.c. |
| Antihypertensive | Nifedipine | 57.8 | 10.5 | >100 | n.c. | >100 | n.c. |
| Anesthetic | Midazolam | 87.0 | 12.5 | >220 | n.c. | >220 | n.c. |
| Proton pump inhibitor | Omeprazole | 110 | 46 | >300 | n.c. | >300 | n.c. |
| COX-2 selective inhibitor | Etoricoxib | 130 | 33 | >200 | n.c. | >200 | n.c. |
| Antiasthma | Montelukast | 160 | 16 | >600 | n.c. | >600 | n.c. |
| Hypercholesterolemia | Simvastatin | 209 | 24 | 241 | 55 | >300 | n.c. |
| Proton pump inhibitor | Pantoprazole | 439 | 217 | >500 | n.c. | >500 | n.c. |
| Antibiotic | Sparfloxacin | 529 | 95 | >2000 | n.c. | >2000 | n.c. |
| Antiviral | Saquinavir | >30 | n.c. | >30 | n.c. | >30 | n.c. |
| Antidiabetic | Repaglinide | >100 | n.c. | >100 | n.c. | >100 | n.c. |
| Antihypertensive | Aliskiren | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Antidepressant | Citalopram | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Antiviral | Darunavir | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Antibiotic | Erythromycin | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Heart failure | Eplerenone | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Antihypertensive | Losartan | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Iron chelator | Deferasirox | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| NSAID | Rofecoxib | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| Hypercholesterolemia | Rosuvastatin | >300 | n.c. | >300 | n.c. | >300 | n.c. |
| β-Blocker | Talinolol | >600 | n.c. | >600 | n.c. | >600 | n.c. |
| Hypercholesterolemia | Atorvastatin | >800 | n.c. | >800 | n.c. | >800 | n.c. |
| Antihypertensive | Captopril | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Antibiotic | Levofloxacin | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Obesity | Orlistat | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Insomnia | Ramelteon | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Smoking cessation | Varenicline | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Antidiabetic | Sitagliptin | >1000 | n.c. | >1000 | n.c. | >1000 | n.c. |
| Antiulcerative | Cimetidine | >2000 | n.c. | >2000 | n.c. | >2000 | n.c. |
| NSAID | Meloxicam | >2000 | n.c. | >2000 | n.c. | >2000 | n.c. |
IC50(ER), IC50 values based on digoxin ER; IC50(Papp), IC50 values based on digoxin permeability n.c., not calculated; NSAID, nonsteroidal anti-inflammatory drug; PappAB, substrate (digoxin) permeability from apical to basolateral; PappBA, substrate (digoxin) permeability from basolateral to apical.