Document Detail


A mechanism-based approach for absorption modeling: the Gastro-Intestinal Transit Time (GITT) model.
MedLine Citation:
PMID:  22286919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Absorption models used in the estimation of pharmacokinetic drug characteristics from plasma concentration data are generally empirical and simple, utilizing no prior information on gastro-intestinal (GI) transit patterns. Our aim was to develop and evaluate an estimation strategy based on a mechanism-based model for drug absorption, which takes into account the tablet movement through the GI transit. This work is an extension of a previous model utilizing tablet movement characteristics derived from magnetic marker monitoring (MMM) and pharmacokinetic data. The new approach, which replaces MMM data with a GI transit model, was evaluated in data sets where MMM data were available (felodipine) or not available (diclofenac). Pharmacokinetic profiles in both datasets were well described by the model according to goodness-of-fit plots. Visual predictive checks showed the model to give superior simulation properties compared with a standard empirical approach (first-order absorption rate + lag-time). This model represents a step towards an integrated mechanism-based NLME model, where the use of physiological knowledge and in vitro–in vivo correlation helps fully characterize PK and generate hypotheses for new formulations or specific populations.
Authors:
Emilie Hénin; Martin Bergstrand; Joseph F Standing; Mats O Karlsson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The AAPS journal     Volume:  14     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2013-01-28     Revised Date:  2013-06-13    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155-63     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. Emilie.henin@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Delayed-Action Preparations / administration & dosage,  pharmacokinetics
Diclofenac / administration & dosage,  pharmacokinetics
Felodipine / administration & dosage,  pharmacokinetics*
Gastrointestinal Transit / drug effects,  physiology*
Humans
Intestinal Absorption / drug effects,  physiology*
Models, Biological*
Tablets
Chemical
Reg. No./Substance:
0/Delayed-Action Preparations; 0/Tablets; 15307-86-5/Diclofenac; 72509-76-3/Felodipine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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