METHODS OF TREATING DISEASE WITH DICHLORPHENAMIDE
Provided herein are methods for administering dichlorphenamide, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the subject is also being administered an organic anion transporter-1 (OAT1) substrate to treat an associated disease or disorder. The method comprises administering to the subject a therapeutically effective amount of dichlorphenamide, or a pharmaceutically acceptable salt thereof, and monitoring the subject for signs and symptoms of toxicity and clinical response associated with the OAT1 substrate.
1 - 12 . (canceled)
13 . A pharmaceutical tablet comprising
a pharmaceutically acceptable carrier, and
dichlorphenamide, said dichlorphenamide being an inhibitor of organic anion transporter-1 (OAT1), the OAT1 inhibitor property of dichlorphenamide having been determined by in vitro experiments in accordance with the FDA draft guidance documents for Drug Interaction Studies (FDA 2017),
said tablet being administrable, in an amount of 50 mg to 200 mg daily, to a patient to treat primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis, only after cessation of treatment of said patient with a drug that is sensitive to OAT1 inhibition,
said cessation being to avoid increased plasma concentration of the drug that is sensitive to OAT1 inhibition in said patient.
14 . The pharmaceutical tablet of claim 13 , wherein the drug that is sensitive to OAT1 inhibition is chosen from methotrexate, famotidine, and oseltamivir.
15 . The pharmaceutical tablet of claim 14 , wherein the drug that is sensitive to OAT1 inhibition is methotrexate.
16 . The pharmaceutical tablet of claim 14 , wherein the drug that is sensitive to OAT1 inhibition is famotidine.
17 . The pharmaceutical tablet of claim 14 , wherein the drug that is sensitive to OAT1 inhibition is oseltamivir.
18 . The pharmaceutical tablet of claim 13 , wherein the tablet is administrable, in an amount of 50 mg once daily.
19 . The pharmaceutical tablet of claim 13 , wherein the tablet is administrable, in an amount of 50 mg twice daily.
20 . The pharmaceutical tablet of claim 13 , wherein the tablet is administrable, in an amount of up to 200 mg/day.
21 . The pharmaceutical tablet of claim 13 , wherein the pharmaceutical tablet, upon administration, results in an adverse reaction profile which is better than the adverse reaction profile resulting from the administration of the pharmaceutical tablet without cessation of treatment of said patient with a drug that is sensitive to OAT1 inhibition,
22 . A method of treating primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis in a patient in need thereof, comprising administering to the patient a pharmaceutical tablet of claim 13 .
23 . A pharmaceutical tablet comprising
a pharmaceutically acceptable carrier, and
dichlorphenamide, said dichlorphenamide being an inhibitor of organic anion transporter-1 (OAT1), the OAT1 inhibitor property of dichlorphenamide having been determined by in vitro experiments in accordance with the FDA draft guidance documents for Drug Interaction Studies (FDA 2017),
said tablet being administrable, in an amount of 50 mg to 200 mg daily, to a patient to treat primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis, only after cessation of treatment of said patient with a drug that is an OAT1 substrate,
said cessation being to avoid increased plasma concentration of the drug that is an OAT1 substrate in said patient.
24 . The pharmaceutical tablet of claim 23 , wherein the tablet is administrable, in an amount of 50 mg once daily.
25 . The pharmaceutical tablet of claim 23 , wherein the tablet is administrable, in an amount of 50 mg twice daily.
26 . The pharmaceutical tablet of claim 23 , wherein the tablet is administrable, in an amount of up to 200 mg/day.
27 . The pharmaceutical tablet of claim 23 , wherein concomitant administration of dichlorphenamide and an OAT1 substrate increases the plasma concentration of drug that is an OAT1 substrate.
28 . A method of treating primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis in a patient in need thereof, comprising administering to the patient a pharmaceutical tablet of claim 23 .