A distribution study with C-14-otilonium bromide in the rat: Evidence for selective tropism for large intestine after oral administration

The aim of this study was to determine the plasma levels and the tissue dis tribution of otilonium bromide, measured as total radioactivity, after oral administration of 2 mg/kg of C-14-labeled drug to rats. Radioactivity leve ls were very low in the plasma (ranging from 2.7 ng Eq/ml at 1.5 h to 0.6 n g Eq/ml at 24 h) as compared with those found in the gastrointestinal (GI) tract, indicating negligible systemic otilonium bromide absorption. Results from both quantitative radioluminography of whole body tissue distribution and radioassay of dissected parts of the GI tract carried out with liquid scintillation counting clearly demonstrate the presence of radioactive comp ounds in the walls of the GI tract at all sacrifice times. In the other tis sues and organs examined, radioactivity was only found in trace amounts in the liver. The presence of radioactivity in the GI walls reflected the tran sit kinetics of drug-enriched contents. The radioactivity in large intestin e walls was measurable at otilonium bromide concentrations in the range of micromole equivalents/kg, from 4 to 8 h after drug administration. Total bo dy radioactivity recovery was 95, 101, 24, and 9% at 1.5, 4, 8, and 24 h, r espectively. In conclusion, orally administered C-14-otilonium bromide is p oorly absorbed systemically, as indicated by the very low plasma radioactiv ity levels, but it is able to effectively penetrate into the large intestin e walls, a recognized target for drugs oriented toward irritable bowel synd rome therapy.