Effects of a new orally active dopamine prodrug, docarpamine, on refractory ascites: A pilot study

OBJECTIVE: Refractory ascites is a debilitating condition in patients with cirrhosis. Recently, docarpamine, an orally active dopamine prodrug, was re ported to increase renal blood flow, glomerular filtration, and sodium excr etion. This suggests docarpamine may be useful for the treatment of refract ory ascites. METHODS: In this study, we investigated docarpamine metabolism in cirrhotic patients and its effect on refractory ascites. RESULTS: Blood samples were obtained from seven cirrhotic patients and six healthy subjects after administration of 750 mg docarpamine, and plasma lev els of free dopamine were measured; In healthy subjects, maximum plasma con centration (C-max), time taken to reach C-max (T-max), elimination half-lif e (T-1/2), and area under the plasma concentration-time curve (AUC) of plas ma free dopamine were 76.8 +/- 24.1 ng/ml, 1.3 +/- 0.2 h, 0.8 +/- 0.1 h, an d 97.5 +/- 21.1 ng h/ml, respectively. In patients with cirrhosis, C-max (5 3.1. +/- 24.9 ng/ml), T-1/2 (0.8 +/- 0.1 h), and AUC (100.6 +/- 45.6 ng . h /ml) were no different from healthy subjects when comparing each parameter , whereas T-max (2.7 +/- 0.2) was significantly longer than that of healthy subjects. We treated 10 cirrhotic patients with refractory ascites with do carpamine or placebo and the same dose of diuretics used before hospitaliza tion. After 8 wk of docarpamine treatment, ascites disappeared completely i n three of the five patients and decreased in the remainder. However, in fi ve patients treated with placebo, ascites was not changed or increased, Sid e effects were not observed in any case. CONCLUSIONS: Docarpamine was found to metabolize ill cirrhotic patients as well as in normal subjects and may be an effective treatment for refractory ascites. (Am J Gastroenterol 1999;94:2475-2481, (C) 1999 by Am. Coll. of G astroenterology).