An Integrated Model for Determining Causes of Poor Oral Drug Absorption |
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Authors: | Yu Lawrence X |
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Institution: | (1) Glaxo Wellcome, Inc., Five Moore Drive, Research Triangle Park, North Carolina, 27709;(2) Present address: Food and Drug Administration, Division of Product Quality Research, 5600 Fishers Lane, Rockville, Maryland, 20857. To whom correspondence should be addressed |
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Abstract: | Purpose. To develop an integrated absorption model for estimating the fraction of dose absorbed and determining the causes of poor oral drug absorption.
Methods. Both analytical and numerical methods were used to estimate the fraction of dose absorbed.
Results. An integrated absorption model was developed by considering transit flow, dissolution, and permeation processes, simultaneously. A framework was proposed to determine permeability-, dissolution-, and solubility-limited absorption. Digoxin, griseofulvin, and panadiplon were employed to illustrate the applications of the integrated model in identifying the causes of poor absorption and guiding formulation development.
Conclusions. The integrated absorption model was successfully applied to digoxin, griseofulvin, and panadiplon to estimate the fraction dose absorbed and to roughly determine the causes of poor oral drug absorption. |
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Keywords: | small intestinal transit dissolution permeation absorption modeling |
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