期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 111, 期 1, 页码 197-205出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2021.10.010
关键词
TIM-1 system; Fed state; Paracetamol; Danazol; pH; Bile acids; In vitro-in vivo relationships
资金
- European Union's Horizon 2020 Research and Innovation Programme [674909]
In this study, the environment in TIM-1 luminal compartments was evaluated and compared with data from healthy adults. The results showed that the gastric and duodenal compartments of TIM-1 accurately reflected the luminal conditions in adults, but there was an overestimation of bile acid concentrations. Adjustments in gastric emptying/acid secretion rates and bile acids identities are expected to improve the relevance of luminal conditions in TIM-1 compartments with those in adults.
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 3 h 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. (C) 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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