Читать книгу Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations - Sheila Annie Peters - Страница 26

Amphiphilic compounds (compounds with both acidic and basic groups), with molecular weights >350 Da also have the possibility of being actively transported into the bile and excreted via faces. Biliary clearance can be estimated by determining the concentration of a drug in the bile (C_bile ) collected from a bile‐duct cannulated preclinical species.

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The parent drug in bile is emptied into the duodenal section of the small intestinal tract via the sphincter of Oddi and may be reabsorbed back into the portal vein as it transits down the intestine. This is called the enterohepatic recirculation (EHR). EHR contributes to an increased half‐life of a drug. Some phase II conjugates are also secreted into bile and converted back to parent in the distal small intestine and reabsorbed as parent.

A metabolite of the drug can also be emptied into bile and into duodenum Figure 1.5. Certain phase II metabolites such as glucuronides are emptied into bile and into duodenum, get reconverted to the parent drug by the gut microflora in the distal intestine and are reabsorbed and recirculated. Although the pharmacokinetic profile is very similar to that associated with parent EHR, the measured C_bile for the parent drug in this case would be low, allowing one to distinguish between parent and metabolite EHR.