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 < .05). Results: Serum LPS and plasma iohexol concentrations did not differ between treatments. Fecal calprotectin concentrations differed between treatments (P = .03). The DI varied over time based on the treatment received (P = .03). Coadministration of omeprazole and carprofen significantly increased fecal calprotectin concentration and DI compared to baseline and carprofen alone.

Clinical Features and Risk Factors for Gastrointestinal Complications in Dogs Treated Surgically for Thoracolumbar Intervertebral Disc Extrusion

“…This is consistent with a report in dogs hospitalized in the ICU in which prophylactic administration of gastro-protectants was associated with a significantly increased risk of development of hemorrhagic GI disease ( 35 ). The most common adverse effect associated with PPI administration in dogs is diarrhea ( 42 – 44 ), but other more serious complications including intestinal dysbiosis and subsequent bacterial pneumonia are possible ( 25 , 45 ).…”

“…There is also growing evidence in people and dogs that concurrent administration of PPIs and NSAIDs can increase the risk of GI injury, permeability and inflammation, though this does not necessarily translate to clinical GI signs in all cases ( 45 , 51 , 52 ). While our results demonstrated that more dogs receiving both NSAIDs and prophylactic PPIs developed GI signs (46%) compared to either individually (41 and 30%), this difference was not significant.…”

Survey-Based Analysis of Current Trends for Prescribing Gastrointestinal Protectants among Small-Animal General Practitioners in Portugal

“…Despite the evidence that PPIs are more effective for management of acid-related disorders [ 12 ], our study reveals that a considerable number (16%) of Portuguese GPs consider H 2 RAs as a preferable choice. We hypothesize that this could be related to the following: (1) H 2 RAs can provide immediate clinical relief, while PPIs can take longer to reach a peak of action [ 15 , 17 ]; (2) PPIs are a more recent drug, while H 2 RAs were historically used among the Portuguese veterinary community; (3) H 2 RAs have additional cytoprotective effects such as increased mucus and bicarbonate secretion [ 15 ]; (4) H 2 RAtherapies are well tolerated in dogs and cats, with a good safety profile [ 38 ]; and (5) recent studies show potential adverse effects of long-term PPI therapies in cats [ 39 ], as well as documented interactions of PPIs with other drugs [ 40 ]. Nevertheless, it is important to acknowledge the fact that H 2 RAs are weaker acid suppressants and have proven to be less effective for controlling acid-related problems [ 15 ].…”

Analysis of the gut microbiome in dogs and cats

“… 30 Therefore, abnormal microbial conversion of luminal substrates by normal microbiota can be pathologic, not just changes in bacterial populations. While some of the microbiome changes that likely originate in the small intestine can be detected in fecal samples, as reported for dogs receiving omeprazole, 23 , 31 dogs with EPI, 32 and dogs with chronic enteropathies (CE), 33 , 34 the above limitations should nevertheless be considered when analyzing fecal samples only.…”