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. Typical patients have an activated renin-angiotensin-aldosterone levels as may be indicated by elevated levels of renin and/or aldosterone. Refractory ascites treatable according to the invention are such that patients beginning treatment require large volume paracentesis at a minimum of: (a) 3 times in 60 days, (b) 4 times in 90 days or (c) at least once every 30 days over a 90-day period. The invention also contemplates treating diuretic intractable ascites. Target plasma dopamine levels are disclosed by with dosing with the contemplated dopamine prodrugs may be guided. Preferred dosing is greater that 2250 mg per day, with more preferred doses exceeding 3500 mg per day.