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

Abstract

OBJECTIVE: Refractory ascites is a debilitating condition in patients with cirrhosis. Recently, docarpamine, an orally active dopamine prodrug, was reported to increase renal blood flow, glomerular filtration, and sodium excretion. This suggests docarpamine may be useful for the treatment of refractory 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 levels of free dopamine were measured. In healthy subjects, maximum plasma concentration (C max), time taken to reach C max (T max), elimination half-life (T 1/2), and area under the plasma concentration-time curve (AUC) of plasma free dopamine were 76.8 ± 24.1 ng/ml, 1.3 ± 0.2 h , 0.8 ± 0.1 h, and 97.5 ± 21.1 ng · h /ml, respectively. In patients with cirrhosis, C max (53.1 ± 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 docarpamine or placebo and the same dose of diuretics used before hospitalization. After 8 wk of docarpamine treatment, ascites disappeared completely in three of the five patients and decreased in the remainder. However, in five patients treated with placebo, ascites was not changed or increased. Side effects were not observed in any case. CONCLUSIONS: Docarpamine was found to metabolize in cirrhotic patients as well as in normal subjects and may be an effective treatment for refractory ascites.