Quantitation of biliary excretion of drugs in man.
An experimental model was developed to allow extended investigation (up to3 days) of the kinetics of upper gastrointestinal elimination (including enterohepatic recirculation) of drugs or metabolites in normal subjects under near physiologic conditions. The test drug (100 mg carprofen) was given by mouth or through a triple-lumen nasogastric tube to the upper duodenum to three normal subjects. The amounts of drug and metabolite passing the gastrointestinal aspiration port for each time interval were calculated from the concentrations measured in the aspirate using dual nonabsorbable markers and continuous sampling and reinfusion of intestinal fluids. Crossover studies without intubation in the same subjects and comparisons to historical controls demonstrated that the intubation procedure did not affect normal kinetic data obtained from conventional blood and urine specimens. The model permits direct comparison of gastrointestinal-biliary clearance with renal and with total body clearance and is particularly useful in resolving kinetic questions of gastrointestinal-biliary excretion or recirculation of metabolites when a drug must be taken by mouth. Potential first-pass phenomena may also be investigated by means of incremental gastrointestinal clearance values.[1]References
- Quantitation of biliary excretion of drugs in man. Dujovne, C.A., Gustafson, J.H., Dickey, R.A. Clin. Pharmacol. Ther. (1982) [Pubmed]
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