Differences between the biliary excretion of tri[14C]methyl-1-(3-hydroxyphenyl)ammonium iodide in Wistar and Gunn rats

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Abstract
1. The biliary excretion of [14C]trimophonium iodide [tri[14C]methyl(3-hydroxyphenyl)ammonium iodide] was studied in normal Wistar animals and in jaundiced homozygous Gunn rats. 2. In normal Wistar rats small amounts of radioactivity (approx. 3% of the dose in 4h) were excreted in bile as two glucuronide conjugates, i.e. [14C]trimophonium glucuronide [tri[14C]methyl-(3-oxyphenyl)ammonium glucuronide] (85%) and 3-di[14C]methylaminophenyl glucuronide (10–15%). Only minor amounts of the unchanged drug were detected in bile. 3. In the homozygous jaundiced Gunn rat large amounts of radioactivity (26% of the dose in 4h) were eliminated in bile as [14C]trimophonium glucuronide alone. The quantitative excretion of this metabolite in Gunn rat bile was about ten times that in normal animals. 4. It is proposed that the biochemical lesion in the homozygous Gunn rat may indirectly affect the biliary transport of exogenous glucuronides across the canalicular membrane.