XIPAMIDE DISPOSITION IN LIVER-CIRRHOSIS

The pharmacokinetics of the sulfonamide-type diuretic xipamide was studied in patients with liver cirrhosis and ascites and compared with healthy control subjects. After oral administration of 40 mg xipamide, the diuretic was rapidly distributed in the blood and the ascites. The ratio of the area under the concentration-time curve (AUC) of plasma and ascitic fluid was 7:2, as was the protein content in the respective compartments. The AUC in plasma of cirrhotic patients was significantly greater than in control subjects (p < 0.001). The most striking finding was the increase of the amount (Ae) of parent drug and main metabolite excreted into the urine (p < 0.001). The renal clearance of xipamide was only moderately reduced in patients with liver cirrhosis. Both AUC and Ae were positively correlated to the plasma concentration of direct bilirubin of the patients (p < 0.05). We concluded that nonrenal drug clearance in patients with liver cirrhosis was reduced as a result of the blockage of hepatobiliary excretion during cholestatic conditions.