Andersen, Sophie Susanna Strindberg

Christfort, Juliane Fjelrad

Müllertz, Anette

Nielsen, Line Hagner

Online Research Database In Technology

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Downloaded from orbit.dtu.dk on: Mar 30, 2019Investigation of segmental differences in the gastrointestinal tract of ratsChristfort, Juliane Fjelrad; Andersen, Sophie Susanna Strindberg; Nielsen, Line Hagner; Müllertz, AnettePublication date:2018Document VersionVersion created as part of publication process; publisher's layout; not normally made publicly availableLink back to DTU OrbitCitation (APA):Christfort, J. F., Andersen, S. S. S., Nielsen, L. H., & Müllertz, A. (2018). Investigation of segmental differencesin the gastrointestinal tract of rats. Abstract from Northern Pharma Network Meeting, Odense, Denmark. - 1 - Fig. 1: Schematic of the sampling and pH measurements in the GI tract of a rat in A: Forestomach, B: Glandular stomach, C: Proximal small intestine, D: Distal small intestine, E: Caecum, F: Colon.  Investigation of segmental differences in the gastrointestinal tract of rats  Juliane Fjelrad Christfort1, Sophie Strindberg Andersen1, Line Hagner Nielsen2 and Anette Müllertz1,3 1Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark 2Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345C, 2800 Kgs. Lyngby, Denmark 3Bioneer:FARMA, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark   INTRODUCTION & AIM Different in vitro methods are widely used to predict oral bioavailability of drugs, but to improve the in vitro in vivo correlation (IVIVC), it is important that in vitro data are generated under conditions as close to the in vivo situation as possible. Several simulated gastrointestinal (GI) fluids have been developed to accommodate this need, but they are based on the composition of GI fluids in humans and dogs (1). The aim of the current study was to investigate pH, osmolality, bile acid and phospholipid concentration in different segments of the GI tract in rats, with the overall aim of producing a rat fasted state simulated intestinal fluid (FaSSIF).  METHODS Six male Sprague Dawley rats weighing approximately 300 g were fasted overnight prior to the experiments. The rats were anesthetized, and the abdomen was opened through the midline. The pH was measured with a micro electrode through a small hole in six different segments of the GI tract; forestomach, glandular stomach, proximal small intestine (5 to 20 cm distal to the stomach), distal small intestine (5 to 20 cm proximal to the caecum), caecum and colon (Fig. 1). Fluid samples were collected from the stomach, proximal and distal small intestine, and the osmolality was measured. The concentration of bile acids and phospholipids were determined using a fluorometric and colorimetric enzymatic assay kit, respectively.   RESULTS The pH was measured in six different segments of the GI tract, and the observed values are shown in Table 1. In general, it was possible to determine pH with small standard deviations between the rats, however, the standard deviations observed in the stomach were larger than observed for the other segments. The osmolality in the stomach, proximal and distal small intestine was determined to be 237 ± 19, 313 ± 13 and 328 ± 13 mOsm, respectively. Bile acids and phospholipids were hardly detected in the stomach (1.5 ± 0.9 mM and 0.5 ± 0.5 mM, respectively). In the small intestine, the bile acid concentration was determined to be 24.4 ± 10.5 mM in the proximal part and then increased to 46.8 ± 15.2 mM in the distal part. The phospholipid concentration was similarly higher in the proximal part of the small intestine (2.5 ± 1.7 mM) than in the distal part, where it was hardly detected (0.2 ± 0.3 mM).   Table 1: pH values measured in six different segments of the GI tract (mean ± SD, n=4-6).  Forestomach Glandular stomach Proximal small intestine Distal  small intestine Caecum Colon pH 2.0 ± 0.5 2.9 ± 0.7 7.5 ± 0.3 7.8 ± 0.3 7.6 ± 0.2 7.6 ± 0.2  CONCLUSION & FUTURE PERSPECTIVES Different segments of the rat GI tract were investigated regarding pH, osmolality and bile acid and phospholipid concentration. The obtained data will serve as a valuable platform for development of a rat FaSSIF which may lead towards better IVIVC in the future.  REFERENCES 1. Tanaka, Y.; Baba, T.; Tagawa, K.; Waki, R.; Nagata, S. Prediction of oral absorption of low-solubility drugs by using rat simulated gastrointestinal fluids: the importance of regional differences in membrane permeability and solubility. J Pharm Pharm Sci. 2014, 17(1), 106-20.  

Investigation of segmental differences in the gastrointestinal tract of rats

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Investigation of segmental differences in the gastrointestinal tract of rats

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