title: An in vitro biorelevant gastrointestinal transfer (BioGIT) system for forecasting concentrations in the fasted upper small intestine: Design, implementation, and evaluation.
abstract: OBJECTIVE
  Design an in vitro methodology for studying gastrointestinal transfer in the fasted state and implement the methodology in vitro by using a biorelevant gastrointestinal transfer system(BioGIT); evaluate the usefulness of BioGIT in predicting luminal concentrations of lipophilic weak bases in the fasted upper small intestine.
  
  
  METHODS
  The methodology was designed after modeling existing luminal data. Its implementation in vitro was based on a three compartment setup. Reproducibility of the transfer process was evaluated under conditions where solutions and/or suspensions were present in gastric and/or duodenal compartment and by using ranitidine, dipyridamole, ketoconazole, and posaconazole as model drugs. The transfer process as well as concentrations of dipyridamole, ketoconazole and posaconazole measured in the duodenal compartment were compared with data previously collected in the upper small intestine, after administration of identical preparations/dosage forms to fasted adults.
  
  
  RESULTS
  Using BioGIT, the transfer process was performed reproducibly in all cases (RSD b 12.9%); data with dipyridamole and ketoconazole were in line with luminal data in humans. Dipyridamole, ketoconazole and posaconazole concentrations in duodenal compartment were also in line with previously measured concentrations in the fasted upper small intestine of healthy adults.
  
  
  CONCLUSIONS
  BioGIT system could be useful for the evaluation of the impact of gastrointestinal transfer on concentrations in the upper intestinal lumen during the first hour, after oral administration of dispersing/solution dosage forms of lipophilic weak bases.
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kourentas
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Vertzoni
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Nick
authors.initials: N
authors.lastname: Stavrinoudakis
authors.affiliation: Department of Chemical Engineering, School of Engineering, University of Patras, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Symillidis
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece. Electronic address: simillidou@pharm.uoa.gr.
authors.forename: Mira
authors.initials: M
authors.lastname: Symillides
mesh_terms: D004176:Dipyridamole / Q000378:metabolism*; D005215:Fasting; D005753:Gastric Mucosa / Q000378:metabolism; D041981:Gastrointestinal Tract; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism*; D007654:Ketoconazole / Q000378:metabolism*; D008954:Models, Biological; D011899:Ranitidine / Q000378:metabolism*; D014230:Triazoles / Q000378:metabolism*
chemical_list: D014230:Triazoles; D004176:Dipyridamole; C101425:posaconazole; D011899:Ranitidine; D007654:Ketoconazole
keywords: BioGIT; Biorelevant evaluation; Gastrointestinal transfer; Luminal concentrations; Precipitation; Weak bases