Assessment of biliary excretion in humans using a novel oroenteric tube

Abstract

The biliary tract is an important route of elimination and potential site of toxicity for many xenobiotics. Quantification of biliary excretion in healthy volunteers is logistically challenging and is rarely defined during drug development. The current study uses a novel oroenteric tube to examine the pharmacokinetics of mebrofenin, a compound that undergoes rapid hepatic uptake and extensive biliary excretion. A custom-made multi-lumen oroenteric tube was positioned in the duodenum of four healthy volunteers (3 male, 1 female), subjects were positioned under a gamma camera and 2.5 mCi of 99mTc-mebrofenin was administered intravenously. Duodenal aspirates, blood samples, and urine were collected periodically for 3 h. Sincalide (cholecystokinin-8) was administered intravenously 2 h after mebrofenin to stimulate contraction of the gallbladder, and gamma scintigraphy was used to determine gallbladder ejection fraction. Total body clearance of mebrofenin approximated liver blood flow, and the oroenteric tube efficiently recovered the majority of excreted bile and mebrofenin. When corrected for gallbladder ejection fraction, 77–101% of the dose was recovered. This novel oroenteric tube and clinical protocol provide a useful method to quantify biliary excretion in healthy volunteers. (See Table) Clinical Pharmacology & Therapeutics (2004) 75, P35–P35; doi: 10.1016/j.clpt.2003.11.132 Subject 1 2 3 4 Ejection fraction 0.86 0.82 0.12 0.86 Dose collected in bile (%) 84 66 35 84 Clearance (ml/min/kg) 16.58 17.02 19.88 17.33 Biliary clearance (ml/min/kg) 15.02 11.47 7.81 15.61