Dataset Information

The effect of combined carprofen and omeprazole administration on gastrointestinal permeability and inflammation in dogs.

ABSTRACT: BACKGROUND:Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation. HYPOTHESIS/OBJECTIVES:To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone. ANIMALS:Six healthy adult colony beagle dogs. METHODS:Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3-period design. In the first 7-day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7?days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7?days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey-Kramer post hoc tests (P?

SUBMITTER: Jones SM

PROVIDER: S-EPMC7517840 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The effect of combined carprofen and omeprazole administration on gastrointestinal permeability and inflammation in dogs.

Jones Susan M SM Gaier Ann A Enomoto Hiroko H Ishii Patricia P Pilla Rachel R Price Josh J Suchodolski Jan J Steiner Joerg M JM Papich Mark G MG Messenger Kristen K Tolbert M Katherine MK

Journal of veterinary internal medicine 20200907 5

<h4>Background</h4>Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation.<h4>Hypothesis/objectives</h4>To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and ...[more]

PMID: 32893926

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Project description:Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further investigations into the effects on diseased dogs are needed.

Project description:BackgroundCYP2C19 and CYP3A are the main enzymes involved in omeprazole metabolism, while CYP3A is the principal enzyme family for amlodipine biotransformation. Concomitant use of these drugs in patients with hypertension and acid-related disorders (ARD) might lead to drug-drug interaction.PurposeThe aim of the study was to find if adding omeprazole for treating ARD to amlodipine long-term therapy of hypertension influenced blood pressure of CYP2C19 polymorphism carriers.Patients and methodsFifty-one patients diagnosed with hypertension and ARD were enrolled in the study. Evaluation of antihypertensive therapy was performed by office (OBPM) and ambulatory (ABPM) blood pressure monitoring. Peripheral venous blood was collected for DNA extraction and real-time polymerase chain reaction was performed for CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893) and CYP2C19*17C-806T (rs12248560) polymorphisms analysis.ResultsOf 51 patients there were 21 extensive metabolizers (EMs), 18 ultrarapid metabolizers (UMs) and 12 intermediate metabolizers (IMs). The results of OBPM showed that antihypertensive effect was significantly more pronounced in IMs compared to EMs or UMs and the average group value in the following parameters: average office systolic blood pressure (BP), dynamics of the average office systolic BP. According to dynamics of diastolic BP, the antihypertensive effect was also significantly higher in IMs than in UMs and the average group value. The results of ABPM revealed that there was a significantly more pronounced antihypertensive effect in IMs compared to all other analyzed groups according to the dynamics of both daytime systolic and 24 hr diastolic BP. The average daytime diastolic BP and its dynamics, the average 24 hr systolic BP and its dynamics were higher in IMs compared to EMs and UMs.ConclusionAdding omeprazole to long-term amlodipine therapy in patients with hypertension and ARD may lead to a significantly more pronounced antihypertensive effect in patients genotyped CYP2C19 IMs.

Project description:BackgroundPimobendan is widely used for the treatment of dogs with heart failure via the oral route. A new injectable form of pimobendan is now available and its potential usefulness via intravenous route has been recently demonstrated in dogs. However, the cardiovascular effects of intramuscular (IM) administration of injectable pimobendan have not been investigated yet.HypothesisIM administration of pimobendan may have the same hemodynamic effect as the IV route.MethodsSix healthy Beagle dogs underwent a placebo-controlled double-blind crossover study. The early cardiovascular effects after a single dose of IM and IV injections of pimobendan (0.2 ml/kg; Pimo IM and Pimo IV, respectively) were compared to the same volume of IM placebo (Saline IM) in anesthetized dogs. Clinical [heart rate (HR) and blood pressure (BP)] and echocardiographic hemodynamic parameters [left ventricular (LV) inflow waveforms of diastolic early wave (eV), atrial systolic wave (aV), diastolic early mitral ring velocity (e'), peak velocity (pV), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR)] were monitored with 15 min intervals for 120 min.ResultsDiastolic BP decreased significantly at 30 min in Pimo IM compared to Saline IM. Mean eV and CO values significantly increased from 75 min, e' from 60 min, pV from 75 min, and SV from 15 to 120 min, whereas SVR significantly decreased at 30-60 min in Pimo IM compared to those of Saline IM (P < 0.05). Compared with the Pimo IV, eV and pV were significantly lower at 30-60 min (P < 0.05) while SV was significantly higher at 90-105 min in Pimo IM (P < 0.05). Other hemodynamic parameters (BP, HR, SVR, CO, e', and E/e') did not significantly change between Pimo IM and IV.ConclusionsThe hemodynamic effect of pimobendan following IM and IV injection was described. Our results suggested that IM administration of pimobendan is equally comparable and possibly interchangeable with IV administration. This warrant further studies to investigate the clinical effectiveness of IM pimobendan in treating dogs with congestive heart failure or in heart failure cases unable to receive IV or oral administration.

Dataset Information

The effect of combined carprofen and omeprazole administration on gastrointestinal permeability and inflammation in dogs.

Publications

The effect of combined carprofen and omeprazole administration on gastrointestinal permeability and inflammation in dogs.

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