An integrated model for determining causes of poor oral drug absorption.
OBJECTIVE
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.
Yu
L X
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Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA. yul@cder.fda.gov
D000284:Administration, Oral; D000465:Algorithms; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics; D005746:Gastric Emptying; D006118:Griseofulvin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008962:Models, Theoretical; D010069:Oxadiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D010316:Particle Size; D010539:Permeability; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D011810:Quinoxalines / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility
D014151:Anti-Anxiety Agents; D000935:Antifungal Agents; D002316:Cardiotonic Agents; D010069:Oxadiazoles; D011810:Quinoxalines; D006118:Griseofulvin; D004077:Digoxin; C069443:panadiplon