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The metabolic inhibition model which predicts the intestinal absorbability and metabolizability of drug: Theory and experiment

External protocol Created on 10 Apr 2014

Authors

Takashi Mizuma, Shoji Awazu

Summary

The intestinal absorption of analgesic peptides (leucine enkephalin and kyotorphin) and modified peptides in rat were studied. Although these peptides were not absorbed, the absorbability (absorption clearance) of these peptides were increased in the presence of peptidase inhibitors. In order to kinetically analyze these phenomena, we proposed the metabolic inhibition model, which incorporated the metabolic clearance (metabolizability) with the absorption clearance. Metabolic activity was determined with intestinal homogenates. The higher the metabolic clearance was, the lower was the absorption clearance. The relationships between the absorption clearance and the metabolic clearance of the experimental data as well as of the theoretical values were hyperbolic. This model predicted the maximum absorption clearances of cellobiose-coupled leucine enkephalin (0.654 µl/min/cm) and kyotorphin (0.247 µl/min/cm). Details of the experimental methods are described.

Further details

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