Evaluation of gastrointestinal motility directly from human pharmacokinetic data

Since the 1980s, a considerable body of research has been dedicated to the development of in silico models for the prediction of human pharmacokinetic data based on absorption in a series of discreet intestinal compartments. While some of these models have been successfully used to predict future pharmacokinetic results or to explain previous results, evidence for compartmental absorption in individual pharmacokinetic data has not been published. This article presents in vivo evidence for compartmental drug absorption along with an empirical method for determining gastrointestinal (GI) tract location during absorption, using individual time–absorption rate profiles. Comparisons are shown between the absorption rate profiles and corresponding gamma scintigraphy images, to demonstrate the reliability of the GI position assignments and a hypothesis is proposed to explain the appearance of peaks and troughs in absorption rate profiles. Absorption rate analysis is shown to be a reliable and low cost tool for interpretation of unexpected pharmacokinetic data. Pharmaceutical scientists should find it useful for understanding the in vivo performance of drug products and it is hoped this will result in fewer delays and lower costs during drug development programs.

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