Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

Abstract

Key Points• Understanding conditions of gastrointestinal dysmotility and impaired GI-transit requires accurate noninvasive techniques to monitor the precise location of ingested content.• We demonstrate a non-invasive high resolution X-ray imaging technique to track transit of solid material in vivo, under two specific pharmacological treatment conditions.• Our data indicate GI tract region-specific effects of the modulatory drugs on transit of contents.• We provide evidence that loperamide slows stomach emptying and GI transit, and that prucalopride increases stomach emptying and accelerates colonic transit in aged rats. AbstractBackground Dysmotility in the gastrointestinal (GI) tract often leads to impaired transit of luminal contents leading to symptoms of diarrhea or constipation. The aim of this research was to develop a technique using high resolution X-ray imaging to study pharmacologically induced aged rat models of chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation. The 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonist prucalopride was used to accelerate transit, and the opioid agonist loperamide was used to delay transit. Methods Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or loperamide (in dimethyl sulfoxide, DMSO) for 7 days by continuous 7-day dosing. To determine the GI region-specific effect, transit of six metallic beads was tracked over 12 h using high resolution X-ray imaging. An established rating scale was used to classify GI bead location in vivo and the distance beads had propagated from the caecum was confirmed postmortem. Key Results Loperamide (1 mg/kg) slowed stomach emptying and GI transit at 9 and 12 h. Prucalopride (4 mg/kg) did not significantly alter GI transit scores, but at a dose of 4 mg/kg beads had moved significantly more distal than the caecum in 12 h compared to controls. Conclusions & Inferences We report a novel high-resolution, non-invasive, X-ray imaging technique that provides new insights into GI transit rates in live rats. The results demonstrate that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit.

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

“…Data in the literature on the gastric emptying of solid oral dosage forms in rats is contradictory. A number of studies have reported the failure of capsules to empty from the stomach [18,19], albeit other investigations have demonstrated the transit of solid oral dosage forms through the GI tract [13,20,21]. These contradictory findings are difficult to interpret and may be related to a multitude of factors.…”

“…As such, to better understand intestinal transit, non-invasive imaging techniques have been employed to visualise drug delivery systems along the GI tract [20][21][22][23][24]. Techniques such as magnetic resonance imaging (MRI) [25], single-photon emission computed tomography (SPECT) [13] and X-ray imaging [26] have been applied to track the intestinal movement of solid dosage forms following oral administration.…”

Effect of N‐palmitoylethanolamine‐oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease

“…The methods used for measuring GI transit have been described in detail previously by Dalziel et colleagues. [22][23][24]…”

PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents

“…The gastric emptying or retention of orally-administered dosage forms in rodent models are currently poorly understood and are subject to varying parameters such as: gastric mobility (Dalziel et al 2017), size of dosage form (Dalziel et al 2016), the effect of anaesthesia (Yamashita et al 2011) and potentially pre-or post-prandial states (Mori 1989), to name a few. A study, for example, demonstrated that enteric-coated gelatine size 9 capsules were able to empty from the stomach of a rat between 2 to 8h after administration (Albrecht et al 2006).…”