Does the rat have an empty stomach after an overnight fast?

Jeffrey, Philip D.; Burrows, M. R.; Bye, Anja

doi:10.1258/002367787781363444

Cited by 11 publications

(2 citation statements)

References 6 publications

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“…A limiting ridge, a thickened portion of lamina propria, separates these portions (Kararli, 1995;DeSesso and Jacobson, 2001). This limiting ridge and dual-portioned stomach may account for why food is present in the rat stomach after a 12-hour fast, whereas the human stomach is over 90% empty after only 4 hours of fasting (Read et al, 1986;Jeffrey et al, 1987). Also, the duodenum, jejunum, and ileum make up 4%, 38%, and 58% of the small intestine, respectively, in humans and 8%, 90%, and 2% of the small intestine in rats.…”

Section: Discussionmentioning

confidence: 99%

Predicting Impact of Food and Feeding Time on Oral Absorption of Drugs with a Novel Rat Continuous Intestinal Absorption Model

2022

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Intricacies in intestinal physiology, drug properties, and food effects should be incorporated into models to predict complex oral drug absorption. A previously published human continuous intestinal absorption model based on the convection-diffusion equation was modified specifically for the male Sprague-Dawley rat in this report. Species-specific physiologic conditions along intestinal lengthexperimental velocity and pH under fasted and fed conditions, were measured and incorporated into the intestinal absorption model. Concentration-time (C-t) profiles were measured upon a single intravenous and peroral (PO) dose for three drugs: amlodipine (AML), digoxin (DIG), and glyburide (GLY). Absorption profiles were predicted and compared with experimentally collected data under three feeding conditions: 12-hour fasted rats were provided food at two specific times after oral drug dose (1 hour and 2 hours for AML and GLY; 0.5 hours and 1 hour for DIG), or they were provided food for the entire study. Intravenous versus PO C-t profiles suggested absorption even at later times and informed design of appropriate mathematical input functions based on experimental feeding times. With this model, AML, DIG, and GLY oral C-t profiles for all feeding groups were generally well predicted, with exposure overlap coefficients in the range of 0.80-0.97. Efflux transport for DIG and uptake and efflux transport for GLY were included, modeling uptake transporter inhibition in the presence of food. Results indicate that the continuous intestinal rat model incorporates complex physiologic processes and feeding times relative to drug dose into a simple framework to provide accurate prediction of oral absorption. SIGNIFICANCE STATEMENTA novel rat continuous intestinal model predicts drug absorption with respect to time and intestinal length. Feeding time relative to dose was modeled as a key effect. Experimental fasted/fed intestinal pH and velocity, efflux and uptake transporter expression along intestinal length, and uptake transporter inhibition in the presence of food were modeled. The model uses the pharmacokinetic profiles of three model drugs and provides a novel framework to study food effects on absorption.

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Section: Discussionmentioning

confidence: 99%

Predicting Impact of Food and Feeding Time on Oral Absorption of Drugs with a Novel Rat Continuous Intestinal Absorption Model

2022

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“…In consideration of this fact, it must be known how long the animal can be starved without any harm to its welfare. For instance, Jeffrey et al (1987) observed variable amounts of food in the stomachs of male rats following an overnight fast and noted that the diet type and diet regimen can result in variable quantities of food being retained in the stomach after fasting overnight. However, Schlingmann et al (1997) found that the stomach of rats fasting 6, 12 and 18 hours was almost empty and that only rats fasted for 6 hours did not show any distress.…”

Section: Oral Administration (Per Os}mentioning

confidence: 99%