Title:
In vitro simulation of the environment in the upper gastrointestinal lumen after drug administration in the fed state using the TIM-1 system and comparison with luminal data in adults
Languages of Item:
English
Abstract:
We evaluated the environment in TIM-1 luminal compartments using paracetamol and danazol solutions and suspensions and the fed state configuration. Data were compared with recently published data in healthy adults. TIM-1 Experiments were performed with a 3-fold downscale. Volumes of secretions in gastric and duodenal compartments adequately reflected the luminal data in adults up to 3h post drug dosing. pH values in duodenal and jejunal compartments adequately reflected average pH values in adults. In gastric compartment pH values where initially higher than average values in adults and reached baseline levels earlier than in adults. The environment in the TIM-1 gastric compartment and jejunal compartment adequately reflected the average total paracetamol and danazol amounts per volume of contents in the adult stomach and upper small intestine, respectively. Total bile acids concentrations in the micellar phase of contents in duodenal and jejunal compartments overestimated micellar concentrations in the upper small intestine of adults. Adjustments in gastric emptying / acid secretion rates and bile acids identities in the duodenal and jejunal compartments, and application of dynamic bile acids secretion rates are expected to further improve the relevance of luminal conditions in TIM-1 compartments with those in adults.
Authors:
Christina Pentafragka
Irena Tomaszewska
Susann Bellmann
Mans Minekus
Ronald Schilderink
Maria Vertzoni
Mark McAllister
Christos Reppas
Keywords:
TIM-1 system, fed state, paracetamol, danazol, pH, bile acids, in vitro-in vivo relationships
Main subject category:
Health Sciences
Project information:
This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 674909 (PEARRL).
