Spironolactone and enzyme induction in patients with alcoholic cirrhosis

Abstract

The present study was undertaken to determine whether or not spironolactone could induce drug-metabolizing enzymes in patients with ascites due to alcoholic cirrhosis of the liver. The disposition of antipyrine was therefore studied in 15 patients with cirrhosis before and after 13 days of spironolactone treatment (200 mg/day) and in 15 comparable patients not treated by spironolactone. In spironolactone-treated patients, a 40% increase in elimination rate constant of antipyrine (P less than 0.01) was due both to a decrease in apparent volume of distribution by 11% (P less than 0.01) and to a 20% rise in metabolic clearance rate (P less than 0.01). In control patients treated with furosemide or by paracentesis no significant change in metabolic clearance rate of antipyrine was found. As with spironolactone, furosemide decreased the apparent volume of distribution (9%, P less than 0.05) in proportion to the loss in body weight. Since spironolactone treatment was not associated with improvement in the fractional clearance of bromosulfophthalein, nor in serum albumin, prothrombin time, and factor V, the data are compatible with the idea that even in cirrhosis the hepatic drug-oxidizing enzymes were induced by spironolactone. Thus, the consequences of enzyme induction should be considered when spironolactone is associated with other drugs for the treatment of cirrhotic patients.