Characterization of gastrointestinal transit and luminal conditions in pigs using a telemetric motility capsule
Autor: | Laura J. Henze, René Holm, Harriet Bennett-Lenane, Brendan T. Griffin, Werner Weitschies, Felix Schneider, Mirko Koziolek, Niklas J. Koehl, Michael Grimm |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
Swine Landrace pig male Pharmaceutical Science Physiology Stomach emptying 02 engineering and technology Intestine transit time Biology 030226 pharmacology & pharmacy Beagle 03 medical and health sciences Dogs 0302 clinical medicine Pharmacokinetics In vivo medicine Animals Telemetry Gastrointestinal Transit Cross-Over Studies Gastric emptying Stomach Temperature 021001 nanoscience & nanotechnology Product development medicine.anatomical_structure Postprandial Gastric Emptying Gastrointestinal transit Digestion Stomach pH Gastrointestinal Motility 0210 nano-technology Intestine motility |
Zdroj: | European Journal of Pharmaceutical Sciences |
Popis: | Within preclinical research, the pig has become an important model in regulatory toxicology and pharmacokinetics, to assess oral dosage forms and to compare different formulation strategies. In addition, there are emerging application of the pig model to asses clinical dosing conditions in the fasted and fed state. In this study, the gastrointestinal transit conditions in male landrace pigs were studied with a telemetric motility capsule under fasted and postprandial conditions. The whole gut transit time (WGTT) was determined by administering a SmartPill® capsule to four landrace pigs, under both fasted and fed state conditions in a cross-over study design. Overall, this study found that small intestinal transit in landrace pigs ranged from 2.3 – 4.0 h, and was broadly similar to reported human estimates and was not affected by the intake conditions. Gastric emptying was highly variable and prolonged in landrace pigs ranging from 20 – 233 h and up to 264 h in one specific case. Under dynamic conditions pigs have a low gastric pH comparable to humans, however a high variability under fasted conditions could be observed. The comparison of the data from this study with a recent similar study in beagle dogs revealed major differences between gastric maximum pressures observed in landrace pigs and dogs. In the porcine stomach maximum pressures of up to 402 mbar were observed, which are comparable to reported human data. Intestinal maximum pressures in landrace pigs were in the same range as in humans. Overall, the study provides new insights of gastrointestinal conditions in landrace pigs, which can lead to more accurate interpretation of in vivo results obtained of pharmacokinetic studies in preclinical models. While small intestinal transit conditions, GI pH and pressures were similar to humans, the prolonged gastric emptying observed in pigs need to be considered in assessing the suitability of the pig model for assessing in vivo performance of large non-disintegrated oral drug products.. |
Databáze: | OpenAIRE |
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