Evaluation of the Effect of Orally Administered Acid Suppressants On Intragastric pH in Cats

BackgroundEsomeprazole is an S‐enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.ObjectiveTo determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).AnimalsSeven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.MethodsBoth studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.ResultsThe bioavailability of esomeprazole administered as PO enteric‐coated granules and as SC injections was 71.4 and 106%, respectively. The half‐life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).ConclusionThe PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

“…Twenty‐four hours prior to the end of the omeprazole study period (day 60), pH capsules were placed in the stomach of a subset of cats (n = 2) in order to provide a preliminary evaluation of the effect of abrupt drug withdrawal on feline gastric pH following prolonged omeprazole administration. Immediately before placement, the pH capsule and 2 receivers were calibrated with commercial buffer solutions (pH 1.07 and 7.01) as previously described . Following performance of the DEXA scan, while the cat was still heavily sedated, a pH capsule, preassembled with its catheter delivery system, was introduced blindly into the cat's stomach transorally.…”

Section: Methodsmentioning

confidence: 99%

“…Short‐term administration (<8 days) of omeprazole is well‐tolerated in dogs and cats . Few adverse effects, with the exception of self‐limiting diarrhea, have been described with short‐term PPI administration .…”

mentioning

confidence: 99%

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A Prospective, Placebo‐Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats

Gould

Clements

Reed

et al. 2016

Self Cite

BackgroundChronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats.ObjectivesProlonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats.AnimalsSix healthy adult DSH cats.MethodsIn a within subjects, before and after design, cats received placebo followed by omeprazole (0.83–1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two‐way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole.ResultsNo significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole.Conclusions and Clinical ImportanceAlthough further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

“…In published studies in healthy dogs and cats, omeprazole has proven to be more effective at raising intragastric pH than famotidine and is often recommended for the treatment of erosive and ulcerative GI disease . Despite this, famotidine continues to be widely used in veterinary medicine and there might be good reasons behind this practice.…”

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confidence: 99%

Repeated Famotidine Administration Results in a Diminished Effect on Intragastric pH in Dogs

Tolbert

Graham

Odunayo

et al. 2016

Self Cite

BackgroundFamotidine is an acid suppressant commonly administered to dogs. Prolonged famotidine use in people results in decreased efficacy, but the effect in dogs is unknown.Hypothesis/ObjectivesTo compare the effect of repeated oral administration of famotidine or placebo on intragastric pH and serum gastrin in dogs. We hypothesized that famotidine would have a diminished effect on intragastric pH on day 13 compared to day 1.AnimalsSix healthy adult colony Beagles.MethodsRandomized, 2‐factor repeated‐measures crossover design. All dogs received oral placebo or 1.0 mg/kg famotidine q12h for 14 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH on treatment days 1–2 and 12–13. Mean pH as well as mean percentage time (MPT) that intragastric pH was ≥3 or ≥4 were compared between and within groups by analysis of variance. Serum gastrin was measured on days 0, 3, and 12 for each treatment.ResultsContinued administration of famotidine resulted in a significant decrease in mean pH, MPT ≥3, and MPT ≥4 (P < .0001) on day 12 and 13. This resulted in a mean decrease in pH by 1.63 on days 12 and 13 compared to days 1 and 2. Furthermore, a mean decrease of MPT ≥3 and MPT ≥4 by 33 and 45% was observed for the same time period, respectively.Conclusions and Clinical ImportanceContinued administration of famotidine results in a diminished effect on intragastric pH in dogs. Caution is advised when recommending long‐term, daily oral administration of famotidine to dogs.