Bioavailability of Bound Residues

The bioavailability of the radiolabeled bound residues of (XVI) and (XVII) is being investigated following oral administration to bile duct-cannulated rats. The outcomes of these studies are still being analyzed and only initial results are presented. Experiments were conducted in accordance with the UK Home Office regulations for animal welfare. 

A sample of the C-labeled debris was formulated for dosing, as a slurry, in 0.5% aqueous carboxymethyl cellulose. Bile duct-cannulated rats (3 per sex per residue) were given two oral gavage doses, 8 hours apart, of the dose formulation to give 

For (XVI), absorption of radioactivity was minimal with the majority (ca. 95%) of the dose being present in feces. Results to date indicate that the absorption of radioactivity from (XVII) bound residues is slightly higher than those from (XVI). 

Benzoic acid glucose conjugate exhibits acyl migration. 

Permeability of sugar conjugates is predicted to be low by CACO-2 cell line measurements. 

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