Literature DB >> 30703546

Characterization of the GI transit conditions in Beagle dogs with a telemetric motility capsule.

Mirko Koziolek1, Michael Grimm1, Tabea Bollmann1, Kerstin J Schäfer2, Simone M Blattner2, Ralf Lotz2, Georg Boeck2, Werner Weitschies3.   

Abstract

In preclinical research, Beagle dogs are an important model for formulation development and for evaluation of food effects on drug absorption. In this study, the gastrointestinal transit conditions in Beagle dogs were studied with a telemetric motility capsule at different intake conditions. In a cross-over study design, the SmartPill® was given to six Beagle dogs to measure transit times, pH values, pressures and temperatures in the different parts of the canine GI tract. Moreover, the effects of commonly applied pre-treatments as with pentagastrin and famotidine on GI transit conditions were investigated. The gastric transit time in fasted state was short (0.57 ± 0.37 h) and only slightly affected by the pre-treatments. In fed state, gastric transit was clearly prolonged (2.94 ± 0.91 h). The mean intestinal transit time was in the range of 1-2 h and not affected by the intake conditions. The gastric pH values in fasted and fed Beagle dogs were highly variable, but pre-treatment with pentagastrin and famotidine clearly decreased variability. Pre-treatment with pentagastrin resulted in minimum pH values around 0.5 pH units lower than without pre-treatment. Oral administration of famotidine led to constantly elevated pH values of pH 7-8. The maximum pressures in the canine GI tract did not vary significantly between the study arms and typically, maximum pressures of up to 800 mbar were observed in the stomach. The comparison of the data from this study with recent SmartPill® data from humans revealed that major differences could be observed with respect to gastric transit times in fed state, small intestinal transit times as well as maximum pressures arising during GI transit. These differences should be kept in mind if the dog model is used to assess the in vivo performance of solid oral dosage forms intended for use in humans.
Copyright © 2019 Elsevier B.V. All rights reserved.

Entities:  

Keywords:  Animal model; Beagle dog; Food effect; Gastrointestinal transit; Luminal pH; Oral biopharmaceutics; Preclinical species; Wireless motility capsule; pH dependent absorption

Mesh:

Substances:

Year:  2019        PMID: 30703546     DOI: 10.1016/j.ejpb.2019.01.026

Source DB:  PubMed          Journal:  Eur J Pharm Biopharm        ISSN: 0939-6411            Impact factor:   5.571


  8 in total

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5.  Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs.

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6.  Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics.

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Review 8.  From Chihuahua to Saint-Bernard: how did digestion and microbiota evolve with dog sizes.

Authors:  Charlotte Deschamps; Delphine Humbert; Jürgen Zentek; Sylvain Denis; Nathalie Priymenko; Emmanuelle Apper; Stéphanie Blanquet-Diot
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  8 in total

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