Improved oral dosing technique for rats

Conybeare, G.; Leslie, G.B.

doi:10.1016/0160-5402(88)90031-9

Cited by 11 publications

(14 citation statements)

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“…Oral gavage with 1.5 g/kg of glucose was performed followed by glucose testing at baseline (before the gavage) and 20, 60, and 90 minutes after the gavage as described by Conybeare and Leslie. 14 A drop of blood was then obtained from the tip of the tail and glucose was measured using a glucometer on site (True Track Smart System; Home Diagnostic Inc., Fort Lauderdale, FL).…”

Section: Methodsmentioning

confidence: 99%

The utility of [11C] dihydrotetrabenazine positron emission tomography scanning in assessing β-cell performance after sleeve gastrectomy and duodenal-jejunal bypass

Inabnet

Milone

Harris

et al. 2010

Surgery

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Background The aim of this study was to evaluate the effect of sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB) on glucose homeostasis and to evaluate the utility of positron emission tomography (PET) scanning for assessing β-cell mass. Methods Goto-Kakizaki rats were divided into 4 groups: control, sham, SG, or DJB. Oral glucose tolerance, insulin, and glucagon-like peptide-1 (GLP-1) were measured before and after surgery. Before and 90 days after treatment, [11C] DTBZ micro PET scanning was performed. Results The control and sham animals gained more weight compared with SG and DJB animals (P ≤ .05). Compared with control animals, the glucose area under the curve was lower in DJB animals 30 and 45 days after operations (P ≤ .05). At killing, GLP-1 levels were greater in the DJB group compared with sham and SG (P ≤ .05), whereas insulin levels were greater in both DJB and SG compared with sham (P ≤ .05). With PET scanning, the 90-day posttreatment mean vesicular monoamine transporter type 2 binding index was greatest in the DJB animals (2.45) compared with SG (1.17), both of which were greater than baseline control animals (0.81). Conclusion In type 2 diabetic rodents, DJB leads to improved glucose homeostasis and an increase in VMAT2 density as measured by PET scanning.

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Section: Methodsmentioning

confidence: 99%

The utility of [11C] dihydrotetrabenazine positron emission tomography scanning in assessing β-cell performance after sleeve gastrectomy and duodenal-jejunal bypass

Inabnet

Milone

Harris

et al. 2010

Surgery

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“…Micro-aspiration of the protein-containing test solution or vagally mediated reflex bronchospasms due to the gavage could lead to the observed changes (Conybeare and Leslie, 1988). There also may be an association between gastro-esophageal reflux and an accumulation of alveolar macrophages (Nussbaum et al, 1987).…”

Section: Subchronic (13-week) Oral Toxicity In Ratsmentioning

confidence: 99%

Safety evaluation of an α-cyclodextrin glycosyltranferase preparation

Bär¹,

Krul

Jonker

et al. 2004

Regulatory Toxicology and Pharmacology

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“…Based on their anatomy, rats are non‐emetic obligate nose breathers (Takeda et al ., 1993), and there is no clear anatomical path for food or the dosing formulation to flow back up and exit via the mouth. As a result, reflux during gavage dosing can result in subsequent back flow of the compound formulation into the nasal cavity and aspiration into the respiratory tract (Conybeare and Leslie, 1988). An inability to clearly differentiate gavage‐related effects from compound‐related toxicity in the first‐in‐human enabling nonclinical studies, can lead to substantial delays in starting clinical phase 1 studies, limitations in dose escalation to pharmacological targets and even program termination.…”

Section: Introductionmentioning

confidence: 99%

Impact of gavage dosing procedure and gastric content on adverse respiratory effects and mortality in rat toxicity studies

Eichenbaum

Damsch

Looszova

et al. 2010

J of Applied Toxicology

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Unscheduled mortality preceded by adverse respiratory clinical signs in rats dosed by oral gavage may not only be caused by technical gavage error or systemic toxicity but may also be caused by gastro-esophageal reflux and subsequent aspiration of high concentrations of drug formulation. In a 3 week oral gavage rat toxicity study for an early drug development compound, preterminal deaths (approximately 20% of animals) at high doses (≥1000 mg kg(-1) ) and concentrations (≥60 mg ml(-1) ) were preceded by recurrent dyspnea, rales or excessive salivation, without evidence of accidental intrapulmonary gavage error. Histological evaluation revealed extensive necrosis and inflammatory changes in the upper respiratory tract, especially in the nasal turbinates and/or nasopharynx. The presence of food particles in inflammatory exudates suggested a retrograde aspiration of stomach content with test formulation via the nasopharyngeal duct into the posterior region of the nose. In contrast, no mortality or adverse respiratory effects were observed in rats following 2 week intravenous administration at comparable exposures or oral gavage administration at lower concentrations (≤20 mg ml(-1) ). In a pharmacology study, the compound caused a dose-dependent increase in gastric content (partly due to inhibition of gastric emptying), providing a pharmacological basis for the suspected gavage-mediated gastroesophageal reflux. Reducing the dose volume and dosing fasted animals substantially reduced or eliminated the respiratory effects and mortality at the high test article concentrations, demonstrating that the adverse effects are related to the gavage method.

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Improved oral dosing technique for rats

Cited by 11 publications

References 0 publications

The utility of [11C] dihydrotetrabenazine positron emission tomography scanning in assessing β-cell performance after sleeve gastrectomy and duodenal-jejunal bypass

The utility of [11C] dihydrotetrabenazine positron emission tomography scanning in assessing β-cell performance after sleeve gastrectomy and duodenal-jejunal bypass

Safety evaluation of an α-cyclodextrin glycosyltranferase preparation

Impact of gavage dosing procedure and gastric content on adverse respiratory effects and mortality in rat toxicity studies

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