Methods of Treating Ascites

Abstract

The invention relates to the treatment of ascites, and especially refractory ascites, with an orally bioavailable prodrug of dopamine. A preferred prodrug of dopamine is docarpamine. In one embodiment treated patients are, prior to treatment, on doses of furosemide >80 mg/day and/or spironolactone >100 mg/day or equivalent doses of an alternative loop-acting and/or distal-acting diuretic. The ascites treated by the invention are typically caused by liver cirrhosis due to alcohol or non-alcoholic fatty liver disease and generally not due to viral hepatitis or primary biliary cholangitis. Preferred dosing is greater that 2250 mg per day, with more preferred doses exceeding 3500 mg per day.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority from U.S. provisional Ser. No. 62 / 936,270, filed 15 Nov. 2019, U.S. provisional Ser. No. 62 / 943,605, filed 4 Dec. 2019 and U.S. provisional Ser. No. 63 / 067,411, filed 19 Aug. 2020.BACKGROUND OF THE INVENTION[0002]Ascites is a pathologic accumulation of fluid within the peritoneal cavity. It is most commonly associated with cirrhosis of the liver (84% of cases), but is also seen with some forms of cancer (6% of cases, most frequently associated with breast, bronchus, ovary, stomach, pancreas and colon cancer), heart failure (3%), tuberculosis (1%), dialysis, pancreatic disease and other conditions (Runyon 1992).[0003]Refractory Ascites (RA) is a serious medical complication of liver cirrhosis that occurs when ascites can no longer be treated with diuretics and salt restriction, and requires additional and repeated clinical intervention, including large volume paracentesis. It is associated with a significan...

AI Technical Summary

Benefits of technology

[0013]In one embodiment, the invention contemplates a method of treating a patient with ascites, comprising administering to said patient a therapeutically effective amount of docarpamine, wherein, prior to said administering, the patient is treated for more than 1 week with doses of furosemide >80 mg/day and/or spironolactone >100 mg/day or equivalent doses of an alternative loop-acting and/or distal

Problems solved by technology

It is associated with a significant shortening of life expectancy, increased use of medical resources, and ultimately is only curable by liver transplantation.

However, as cirrhosis progresses, the escape of fluids overcomes the lymphatic return, leading to progressive accumulation of fluid directly into the peritoneal cavity.

Thus, renal sodium retention mainly occurs proximally to the site of action of both anti-mineralocorticoid and loop diuretics (e.g. spironolactone and furosemide), and this can explain why diuretic treatment becomes unsuccessful in some patients.

At present, the only curative interventio

Images