The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile production is an active secretion process involving separate processes for organic anions, cations, and polar uncharged molecules.

Drugs excreted through the bile typically have molecular weights above 500 Daltons (Da), while those between 300 and 500 Da are excreted via urine and bile. Any decrease in one excretory route compensates for an increase in the other. Drugs with molecular weights under 300 Da are mainly excreted through the kidneys into urine.

In addition to high molecular weight, biliary excretion requires drugs to possess a strongly polar group. Metabolites like glucuronide conjugates are often more polar than the parent drug. The formation of a glucuronide increases the compound's molecular weight by nearly 200 Da, enhancing its polarity.

Examples of drugs excreted into bile include digitalis glycosides, bile salts, steroids, and indomethacin. Compounds that stimulate bile production also boost the biliary excretion of drugs. Phenobarbital could enhance biliary drug excretion by increasing glucuronide metabolite formation and bile flow. Conversely, cholestasis-causing conditions or compounds that reduce bile flow decrease biliary drug excretion. The administration route may also impact the amount of drug excreted into bile.