RT Journal Article SR Electronic T1 Use of the Entero-Test®, a novel approach for the non-invasive capture of biliary metabolites in dogs JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP dmd.109.031062 DO 10.1124/dmd.109.031062 A1 William John Guiney A1 Claire Beaumont A1 Steven Richard Thomas YR 2010 UL http://dmd.aspetjournals.org/content/early/2010/01/28/dmd.109.031062.abstract AB Pre-clinical information on the biliary metabolites of a drug candidate is typically obtained through the collection of bile following surgical cannulation of the bile duct. Here we describe a novel approach using the Entero-Test®, a simple device which facilitates the non-invasive sampling of duodenal bile. The Entero-Test was used to collect bile from six fasted dogs which had been dosed either orally with simvastatin (SV) or intravenously with simvastatin hydroxy acid (SVA), compounds which have been previously reported to undergo extensive metabolism and biliary secretion in the dog. The devices, consisting of a weighted gelatin capsule containing 90 cm of a highly absorbent nylon string, were swallowed by each dog with the proximal end of the string taped to the animal's face. Once the weighted string had reached the duodenum, gallbladder contraction was stimulated in order to release bile. Each bile-stained string was then retrieved via the mouth and, following solvent extraction, samples were analysed for drug-related material by ultra performance liquid chromatography-mass spectrometry and NMR spectroscopy. Numerous metabolites of SV and SVA were observed, and in general, the major metabolites have been reported previously, from studies with bile duct-cannulated animals dosed with [14C]-SV or [14C]-SVA. The results from this study demonstrate the utility of deploying the Entero-Test in absorption, distribution, metabolism and elimination studies, to provide information on the nature of biliary metabolites which, on occasion, may be sufficient to negate the need for more invasive sampling techniques. The benefits and limitations of the technique are discussed.The American Society for Pharmacology and Experimental Therapeutics