The Effect of Drugs on Bile Flow and Composition

Abstract

Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…Several reviews have dealt with the hepatic elimination of drugs and their role in bile formation and cholestasis (Klaassen and Watkins 1984;Okolicsanyi et al 1986;Meijer 1987;Schwenk 1987;Kukongviriyapan and Stacey 1991 ;Meijer and Groothuis 1991). Comparative aspects on various subjects, for example, elimination kinetics (Saville et al 1992), biliary elimination and enterohepatic circulation (Smith 1966(Smith , 1971Levine 1981;Pond and Tozer 1984) and cell models (Blom et al 1982) have been considered by others.…”

Ursodeoxycholic acid promotes intestinal adaptation in a cat model of short bowel syndrome

“…UDCA shows hepatoprotective effects and is currently used clinically in the treatment of a variety of liver disorders [7,8]. In addition, it possesses potent choleretic properties in man and animals [9] and has been employed for the dissolution of gallstones [10]. Although there is some indication that UDCA may alleviate some SBS symptoms [11], the capacity of UDCA to promote specifically the process of intestinal adaptation after intestinal resection has not been investigated.…”

Subchronic Toxicity of Atorvastatin, a Hydroxymethylglutaryl-Coenzyme A Reductase Inhibitor, in Beagle Dogs

“…not unexpected, as the liver is the primary site of cholesterol synthesis and the primary site of drug delivery for HMGRI (1) including AT (3,17). Although transient increases in ALT and AST were described for lovastatin in dogs (up to 180 mg/kg/day) (11) and monkeys (800 mg/kg for 7 days) (12) and for simvastatin (8) (14,17). Hyperplasia and/or inflammation of gallbladder have been described in dogs given other HMGRIs (2,6).…”