Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: Comparison with furosemide

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Abstract
Muzolimine is a loop diuretic with both the dosedepend increasing effectiveness of loop diurexctics 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 reninaldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0−2=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 (AUC0−2=0.28 ± 0.82 vs. 2.69 ± 0.46 mmoles per hr; p<0.005); greater sodium/ chloride excretion ratio (0.45 ± 0.08 vs. 0.26 ± 0.06; p<0.025), and absence of rebound phenomena. These were clearly evident with furosemide, involving both the glomerular filtration rate and renal ion excretions from the third clearance period. Finally, plasma renin activity significantly increased 24 hr after furosemide (from 1.66 ± 0.40 to 2.35 ± 0.60 ng per ml per hr; p<0.05), whereas it was not affected by muzolimine administration. These findings suggest that muzolimine use in the treatment of ascites in cirrhosis may be followed less easily by complications, such as diureticinduced uremia and metabolic alkalosis, as compared to other loop diuretics.