Chapter 16 Routes of Excretion

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Biliary Excretion

The liver secretes 0.25 to 1 liter of bile each day. Some drugs and/or their metabolites are excreted by the liver into bile. Anions, cations, and non-ionized molecules containing both polar and lipophilic groups are excreted into the bile provided that the molecular weight is greater than about 300 Dalton. Molecular weights around 500 Dalton appears optimal for biliary excretion in humans. Lower molecular weight compounds are reabsorbed before being excreted from the bile duct. Conjugates, glucuronides (drug metabolites) are often of sufficient molecular weight for biliary excretion. This can lead to biliary recycling. Indomethacin is one compound which undergoes this form of recycling.

Figure 16.4.1 Enteroheptic Recycling

Figure 16.4.2 Cp versus Time showing a Second Peak

Figure 16.4.2 illustrate plasma concentration versus time curve which may result from extensive enterohepatic recycling. Note, the presence of the second peak shortly after the dumping of bile into the small intestine in response to the presence of food.

Other compounds extensively excreted in bile include cromoglycate (unchanged drug), morphine, and chloramphenicol (as glucuronide). At least part of the biliary secretion is active since bile/plasma concentrations maybe as high as 50/1. There can also be competition between compounds.

The efficiency of this biliary excretion system can be assessed by use of a test substance, such as Bromsulphalein.

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