Simultaneous blood and biliary sampling of esculetin by microdialysis in the rat

Biliary excretion and intestinal reabsorption in enterohepatic circulation play major dispositional roles for some drugs. To circumvent multiple blood sampling and interruption of enterohepatic circulation in conventional bil iary cannulation, the present study utilized the minimally invasive samplin g technique of microdialysis in pharmacokinetics and biliary excretion stud ies. Microdialysis probes were inserted into the jugular vein and bile duct in the anesthetized rat for simultaneous and continuous sampling following intravenous administration of esculetin, a bioactive coumarin derivative. Placements of the microdialysis probes were designed to minimize obstructio n to normal flows of the body fluids. Separation and quantitation of escule tin in the dialysates were achieved using high performance liquid chromatog raphy (HPLC) coupled to UV detection. The results indicated higher drug con centrations in the bile than in the blood, suggesting active biliary excret ion. The study also provided an example of successful application of in viv o microdialysis as an interesting and feasible alternative for pharmacokine tics and biliary drug excretion studies.