L X Yu1. 1. Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA. yul@cder.fda.gov
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.
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.
Authors: Kiyohiko Sugano; Manfred Kansy; Per Artursson; Alex Avdeef; Stefanie Bendels; Li Di; Gerhard F Ecker; Bernard Faller; Holger Fischer; Grégori Gerebtzoff; Hans Lennernaes; Frank Senner Journal: Nat Rev Drug Discov Date: 2010-08 Impact factor: 84.694