METHODS OF TREATING DISEASE WITH DICHLORPHENAMIDE

1 . A method for treating a disease chosen from primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants in a subject in need thereof, wherein the subject is being administered an organic anion transporter-1 (OAT1) substrate for the treatment of a disease or disorder, the method comprising:

discontinuing administration of the OAT1 substrate, and

administering to the subject a therapeutically effective amount of dichlorphenamide, or a pharmaceutically acceptable salt thereof,

thereby avoiding the use of dichlorphenamide, or a pharmaceutically acceptable salt thereof in combination with the OAT1 substrate.

2 . The method of claim 1 , further comprising informing the subject or a medical care worker that co-administration of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, and the OAT1 substrate may result in increased exposure of the OAT1 substrate.

3 . The method of claim 1 , further comprising informing the subject or a medical care worker that co-administration of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, and the OAT1 substrate may result in increased risk of one or more exposure-related adverse reactions associated with the OAT1 substrate.

4 . The method of claim 1 , wherein the therapeutically effective amount of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, is between 25 mg and 200 mg per day.

5 . The method of claim 1 , wherein the therapeutically effective amount of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, is 50 mg twice daily.

6 . The method of claim 1 , wherein the dichlorphenamide, or a pharmaceutically acceptable salt thereof, is administered via a titration scheme that comprises the up-titration of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, at weekly intervals until a modified dose is administered.

7 . The method of claim 6 , wherein the modified dose of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, is 200 mg.

8 . The method of claim 1 , wherein the dichlorphenamide, or a pharmaceutically acceptable salt thereof, is administered via a titration scheme that comprises administering a first dose of the of the dichlorphenamide, or a pharmaceutically acceptable salt thereof, for a period of about one week;

further increasing the dose by an amount equal to an incremental value; and

determining whether the subject tolerates the further increased dose;

wherein the cycle is repeated so long as the subject tolerates the further increased dose, wherein the incremental value at each cycle repetition is the same or different; and

wherein if the subject does not tolerate the further increased dose, the modified dose for the subject is equal to the difference between the further increased dose and the incremental value for the last cycle repetition.

9 . The method of claim 1 , wherein the OAT1 substrate is chosen from a non-steroidal anti-inflammatory drug (NSAID), a beta-lactam antibiotic, a sulfonylurea, and any combination thereof.

10 . The method of claim 1 , wherein the OAT1 substrate is chosen from furosemide, diclofenac, naproxen, bumetanide, captopril, candesartan, losartan, chlorothiazide, cimetidine, ranitidine, telmisartan, olmesartan, simvastatin, fluvastatin, cefaclor, methotrexate, famotidine, oseltamivir, cefadroxil, cefoperazone, ceftizoxime, piperacillin, tazobactam, sulbactam, zidovudine, adefovir, cidofovir, and any combination thereof.

11 . The method of claim 1 , wherein the OAT1 substrate is chosen from furosemide, diclofenac, naproxen, bumetanide, captopril, candesartan, losartan, chlorothiazide, cimetidine, ranitidine, telmisartan, olmesartan, simvastatin, fluvastatin, cefaclor, and methotrexate.

12 . The method of claim 1 , wherein the OAT1 substrate is chosen from methotrexate, famotidine, and oseltamivir.