Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide.
Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days. Renal function was monitored under basal conditions and after diuretic administration through 4-hr clearance periods for 24 hr. The renin-aldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0-12 = 2.52 +/- 0.42 (S.E.) ml per min] and natriuresis (5.14 +/- 1.05 mmoles per hr), which were comparable to those of furosemide (2.85 +/- 0.29 ml per min and 6.75 +/- 1.63 mmoles per hr). Its effect, however, was distributed over a longer period (8 hr) than furosemide (4 hr). Muzolimine activity mainly differed from furosemide because of: significantly lower 12-hr potassium excretion (AUC0-12 = 0.28 +/- 0.82 vs. 2.69 +/- 0.46 mmoles per hr; p less than 0.005); greater sodium/chloride excretion ratio (0.45 +/- 0.08 vs. 0.26 +/- 0.06; p less than 0.025), and absence of rebound phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
D000450:Aldosterone / Q000097:blood; D001201:Ascites / Q000188:drug therapy* / Q000209:etiology; D004232:Diuretics / Q000627:therapeutic use*; D004573:Electrolytes / Q000032:analysis; D005665:Furosemide / Q000627:therapeutic use; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D009156:Muzolimine / Q000627:therapeutic use*; D009994:Osmolar Concentration; D011720:Pyrazoles / Q000627:therapeutic use*; D011897:Random Allocation; D012083:Renin / Q000097:blood
D004232:Diuretics; D004573:Electrolytes; D011720:Pyrazoles; D009156:Muzolimine; D000450:Aldosterone; D005665:Furosemide; D012083:Renin