Drug absorption by the rat jejunum perfused in situ

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Abstract
In anaesthetized rats the rate of appearance of benzoic acid and aminopyrine in jejunal venous blood was measured; the pH of the luminal perfusion solution was varied between 4 and 10.5. The pH-absorption curves were less steep than predicted by the unmodified pH-partition theory. A reduction of the mucosal unstirred layer thickness by means of the segmented-flow technique considerably increased the absorption rate without essentially changing the shape of the pH-absorption curves. The pH at the surface of the jejunal mucosa was 6.0, 6.5, 6.6, and 8.0 for luminal solutions of pH 4.0, 6.0, 8.0, and 10.8, respectively. From the absorption data the microclimate-pH was calculated which would explain best the observed pH-absorption curves. These calculated pH-values correspond well to the values measured at the mucosal surface. Therefore, it was concluded that a microclimate-pH caused the deviation of the intestinal pH-absorption curves of benzoic acid and aminopyrine from the prediction of the unmodified pH-partition theory. The mucosal unstirred layer represented only a considerable permeation resistance and was not responsible for the deviating shape of the pH-absorption curves.

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