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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

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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
Christina Pentafragka Irena Tomaszewska Susann Bellmann Mans Minekus Ronald Schilderink Maria Vertzoni Mark McAllister Christos Reppas
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. (EN)
preprint
Εργασία εν εξελίξει (Preprint) (EL)
Preprint (EN)
Επιστήμες Υγείας (EL)
Health Sciences (EN)
University of Athens
Pergamos Digital Library
Preprint
English
2021-01-01
https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:2964062
uoadl:2964062



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