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Background: To evaluate the efficacy of a single intramuscular adminsitration of long-acting omeprazole (LA-OMEP) in increasing gastric pH in dogs., Hypothesis: We hypothesized that LA-OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration., Animals: Nine healthy research dogs., Methods: Prospective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA-OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined., Results: The mean onset of action for the LA-OMEP was 98.11 min (SD 46.39). The mean number of days the dogs' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3-7) and 5.25 days for MPT pH ≥4 (range, 3-7). Long-acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs., Conclusions and Clinical Importance: The LA-OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Enteric-coated omeprazole capsules are commonly used as a gastric acid suppressant in dogs. However, the efficacy of this formulation has not been evaluated for clinical use in dogs., Hypothesis/objectives: To evaluate the efficacy of a 10 mg PO omeprazole capsule (TriviumVet) undergoing FDA approval to increase gastric pH in dogs. We hypothesized that encapsulated omeprazole would significantly increase the gastric pH compared to placebo and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration., Animals: Six healthy research dogs., Methods: Randomized, blinded, 2-way crossover study. Dogs were PO administered omeprazole at 0.5 to 1.0 mg/kg or placebo (empty gelatin capsules) twice-daily for 5 days. The intragastric pH was recorded on days 2 to 5 of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared between and within treatment groups., Results: Dogs treated with omeprazole had a significantly higher MPT ± SD intragastric pH ≥3 (91.2% ± 11.0%), ≥4 (86.9% ± 13.7%) and mean ± SD pH (5.4 ± 0.8) than dogs treated with placebo (19.7% ± 15.5%, 28.3 ± 20.7, and 2.4 ± 1.0, respectively) (P < .001 for all)., Conclusions and Clinical Importance: The 10 mg enteric-coated omeprazole capsule PO administered evaluated in this study is an effective gastric acid suppressant in healthy dogs., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs., Hypothesis/objectives: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4., Animals: Nine healthy Beagle dogs., Methods: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance., Results: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group., Conclusions and Clinical Importance: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown., Objectives: To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2., Animals: Sixteen healthy cats., Methods: Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance., Results: Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2., Conclusions and Clinical Importance: Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Although the demand for esomeprazole is increasing in veterinary medicine, the pharmacokinetics (PK) and pharmacodynamics of esomeprazole have been described in only a few studies., Objective: To determine the PK of 0.5 and 1 mg/kg esomeprazole administered IV q12h and to investigate its effects on intragastric pH in healthy dogs., Animals: Six adult Beagles., Methods: Open-label, randomized, and crossover design. The dogs received 0.5 or 1 mg/kg esomeprazole IV q12h for 48 hours. Plasma concentrations of esomeprazole were measured by high-performance liquid chromatography-tandem mass spectrometry. Intragastric pH was determined using the Bravo pH monitoring system and recorded as mean percentage time (MPT) for which pH was ≥3 and ≥4 for 24 hours in each group., Results: The peak plasma concentration and area under the curve from the time of dosing to the last measurable concentration in the 1 mg/kg group were higher than those in the 0.5 mg/kg group. However, when the dosage normalized, intergroup differences were not significant. The MPTs for which intragastric pH was ≥3 and ≥4 for 48 hours were 88% ± 7% and 81% ± 9% for the 0.5 mg/kg group and 90% ± 9% and 85% ± 11% for the 1 mg/kg group, respectively, with no significant intergroup differences., Conclusions and Clinical Importance: The pharmacokinetic parameters and acid suppressant effect for 0.5 and 1 mg/kg esomeprazole were not significantly different. Furthermore, the efficacy of esomeprazole 0.5 mg/kg IV q12h was sufficient to increase intragastric pH in Beagles., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Reasons for Performing the Study: Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations., Objectives: To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product., Study Design: Masked 2 period, 2 treatment crossover., Methods: Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6., Results: Treatment significantly (P<0.005) increased gastric pH on Day 5, compared to results obtained prior to treatment (Day -1) and there was no significant difference between products (P = 0.773). Similarly, comparison of median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P = 0.734) did not discriminate between products. Both treatments resulted in significantly lower gastric ulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product., Main Limitations: The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis., Conclusions: ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to OMO and was associated with an equivalent beneficial effect on gastric squamous mucosal ulceration., (© 2017 EVJ Ltd.)

Background: Chronic kidney disease (CKD) is a highly prevalent condition in cats. Advanced CKD is associated with hyporexia and vomiting, which typically are attributed to uremic toxins and gastric hyperacidity. However, gastric pH studies have not been performed in cats with CKD., Hypothesis/objectives: To determine if cats with CKD have decreased gastric pH compared to age-matched, healthy cats. Based on previous work demonstrating an association of hypergastrinemia and CKD, we hypothesized that cats with CKD would have decreased gastric pH compared to healthy, age-matched control cats., Animals: 10 CKD cats; 9 healthy control cats., Methods: All cats with concurrent disease were excluded on the basis of history, physical examination, CBC, plasma biochemistry profile, urinalysis, urine culture, serum total thyroxine concentration, and serum symmetric dimethylarginine concentration (controls only) obtained within 24 hours of pH monitoring and assessment of serum gastrin concentrations. Serum for gastrin determination was collected, and 12-hour continuous gastric pH monitoring was performed in all cats. Serum gastrin concentration, mean pH, and percentage time that gastric pH was strongly acidic (pH <1 and <2) were compared between groups., Results: No significant differences in serum gastrin concentrations were observed between groups (medians [range]: CKD, 18.7 ng/dL [<10-659.0]; healthy, 54.6 ng/dL [<10-98.0]; P-value = 0.713) or of any pH parameters including mean ± SD gastric pH (CKD, 1.8 ± 0.5; healthy, 1.6 ± 0.3; P-value = 0.23)., Conclusions and Clinical Importance: These findings suggest that cats with CKD may not have gastric hyperacidity compared to healthy cats and, therefore, may not need acid suppression. Thus, further studies to determine if there is a benefit to acid suppression in cats with CKD are warranted., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Chronic 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., Objectives: Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats., Animals: Six healthy adult DSH cats., Methods: In 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., Results: No 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 Importance: Although 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., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Evaluation of the radio-transmission pH-measurement system for monitoring the ruminal pH and subacute ruminal acidosis (SARA) in cattle is described. This is done in order to reveal the possible application of this system for detection and pathophysiological research of SARA by continuous ruminal pH measurement. The possibility of using this system for assessment of the ruminal pH in SARA cattle, and the presence of negative correlation between the ruminal pH and ruminal temperature in heathy and SARA cattle were determined. In addition, the 16S rRNA gene pyrosequencing analysis showed that the ruminal microbial community was simpler in SARA cattle, and the bacterial numbers in SARA cattle were lower than those in healthy hay-fed cattle. Concentrate feeding might have reduced the diversity of the ruminal microbial community. Changes in the ruminal microbial community of SARA cattle might be related to the changes in ruminal pH followed by the decrease in the number of some bacteria. Continuous monitoring of the ruminal pH using the radio-transmission pH-measurement system would be applied for detection and prevention of SARA in the field and pathophysiological research of SARA, including ruminal zymology and bacteriology, which have been determined previously by sampling of the ruminal fluid and measuring of ruminal pH., (© 2015 The Authors. Animal Science Journal published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Society of Animal Science.)

An electrode incorporated into a polyethylene hose was introduced under endoscopic control into the stomach of six fasting adult horses for long-lasting pH measurements. The intragastric pH was recorded every four seconds for a period of 24 hours. The Warmblood horses were assigned randomly to receive hay ad libitum (H group); 1.5 kg hay/100 kg BW/day and 1 kg concentrate/100 kg BW/ day (C group) or protocol C plus 75 g pectin-lecithin supplement/100 kg BW/day (P group). The horses were adapted to each diet for 14 days. The 24-hour median pH value for protocol H (2.69) was significantly lower compared to protocol C (3.35) and P (3.44) (p < 0.05). The horses in protocol P had a significant higher percentage (40.1 %) of 24-hour intragastric pH values ≥ 4 than in protocol C (36.2 %) or in protocol H (25.3 %) (p < 0.05).

Background: Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats., Objectives: To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole., Animals: Eight domestic shorthair cats., Methods: Using a randomized 4-way cross-over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo(™) system, starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA., Results: Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice-daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once-daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice-daily omeprazole treatment significantly increased intragastric pH, whereas pH after once-daily omeprazole and ranitidine treatments did not differ from that of placebo-treated cats., Conclusion and Clinical Importance: Only twice-daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

In the present study, three primiparous lactating Holstein cows (260-285 d in lactation) were used in a 3 × 3 Latin square design to assess the effects of three doses (0.0, 0.4 and 0.8 μg/kg body weight) of lipopolysaccharide (LPS, Escherichia coli 0111:B4) on changes in ruminal microbiota and ruminal fermentation. Ruminal pH was linearly decreased (P< 0.001) by LPS challenge, and the concentrations of acetate, propionate, butyrate, total volatile fatty acids and amino N increased linearly (P< 0.001) according to the LPS dose. LPS infusion linearly decreased (P< 0.001) the organic matter degradability of alfalfa hay and soyabean meal in the rumen, but did not affect (P>0.10) the gene expression of Na⁺/K⁺-ATPase and monocarboxylic acid transporter-1, -2 and -4. A plot of principal coordinate analysis based on unweighted UniFrac values and analysis of molecular variance revealed that the structure of ruminal bacterial communities in the control was distinct from that of the ruminal microbiota in the cattle exposed to LPS. At the phylum level, when compared with the control group, LPS infusion in the tested cows linearly increased (P< 0.05) the abundance of Firmicutes, and linearly decreased (P< 0.05) the percentage of Bacteroidetes, Tenericutes, Spirochaetes, Chlorobi and Lentisphaerae. To our knowledge, this is the first study to report that intravenously LPS challenge altered the ruminal bacterial microbiota and fermentation profiles. The present data suggest that systemic LPS could alter ruminal environment and ruminal microbiota composition, leading to a general decrease in fermentative activity.

Reasons for Performing Study: Obesity and gastric ulceration are highly prevalent in horses. Management modifications for preventing squamous gastric ulceration include frequent feeding and free access to pasture; however, these practices may predispose horses to obesity., Objectives: To compare the percentage of hay consumed, intragastric pH and horse activity between feeding from the ground and a hay grid feeder., Study Design: Crossover experimental study., Methods: A pH electrode was inserted into the stomach to record the intragastric pH for 48 h. Horses received 1% of their body weight in grass hay twice a day. Horses were assigned to be fed from the ground or a commercial hay grid feeder for 24 h and then switched to the opposite protocol for an additional 24 h. Horses were continuously video-recorded and the percentage of time spent eating or drinking, walking or standing, and lying down were calculated. Two point data were compared by paired t test and pH over time was compared by repeated measures ANOVA., Results: Horses consumed significantly greater amounts of grass hay when fed on the ground compared with a hay grid feeder (n = 9; P<0.001). There were no significant differences between the groups for mean intragastric pH values (n = 6; P = 0.97), mean intragastric pH over time (n = 6; P = 0.45) the length of time the pH was below 4.0 (n = 6; P = 0.54), and the percentage of time horses spent eating or drinking (n = 9; P = 0.52), walking or standing (n = 9; P = 0.3), or lying down (n = 9; P = 0.4). Within each group horses spent more time eating during the day compared with the night (n = 9; hay grid feeder P = 0.003; ground feeding P = 0.007)., Conclusions: The hay grid feeder studied may be used to reduce the amount of hay ingested by horses without reducing the time horses spend eating., (© 2013 EVJ Ltd.)

Background/aims: Glucocorticoids enhance gastric acid secretion and inhibit gastric cyclooxygenase, thus downregulating formation of PGE2, an inhibitor of gastric acid secretion. In erythrocytes, PGE2 formation is inhibited by annexin 7. The present study thus explored whether annexin 7 participates in the regulation of gastric acid secretion., Methods: Annexin 7 protein expression was determined by Western blotting, cytosolic pH (pHi) of parietal cells utilizing BCECF-fluorescence, and gastric acid secretion by determination of Na(+)-independent pHi recovery from an ammonium pulse (∆pHi/min). Experiments were performed in isolated glands from gene targeted mice lacking annexin 7 (anx7(-/-)) and in respective wild type animals (anx7(+/+))., Results: Prior to treatment pHi and ∆pHi/min were similar in isolated gastric glands from anx7(-/-) and from anx7(+/+) mice. Aspirin (100 µM added to the glands 1 hr prior to the experiment) significantly increased ∆pHi/min to similar values in both genotypes. The administration of dexamethasone (10 µg/g BW subcutaneously for 4 consecutive days prior to the experiments) significantly increased ∆pH/min in anx7(+/+) mice but not in anx7(-/-) mice. Following dexamethasone treatment, the luminal pH was significantly lower and the acid content significantly higher in anx7(+/+) mice than in anx7(-/-) mice. An increase of extracellular K(+) concentration to 35 mM (replacing Na(+)/NMDG(+)) significantly increased ∆pHi/min in both genotypes. In neither genotype dexamethasone increased ∆pH/min further in the presence of 35 mM K(+) or presence of aspirin., Conclusions: Annexin 7 is required for the stimulation of gastric acid secretion by glucocorticoids., (© 2013 S. Karger AG, Basel.)

Background: Little is known about the efficacy of commonly used acid suppressants on intragastric pH in dogs., Objective: To compare the effect of oral famotidine, 2 formulations of omeprazole, and placebo on intragastric pH in dogs with a catheter-free, continuous pH monitoring system., Animals: Six healthy adult mixed-breed colony dogs., Methods: Utilizing a randomized, 4-way cross over, open-label study, dogs were administered famotidine PO (1.0-1.3 mg/kg q12h), omeprazole tablet (1.5-2.6 mg/kg q24h), omeprazole reformulated paste (RP) (Gastrogard, 1.5-2.6 mg/kg q24h), and placebo for 7 days followed by a 10-day washout period. Radiotelemetric pH capsules were placed with gastroscopy assistance to continuously record intragastric pH for 4 days (days 4-7 of dosing). The percentage of time that intragastric pH was ≥3 and ≥4 was compared among treatment groups using repeated measures of analysis of variance. Tukey's Studentized range test was used to determine which groups were different with α= 0.05., Results: Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 22 ± 8% and 14 ± 6% for famotidine, 63 ± 14% and 52 ± 17% for omeprazole tablet, 54 ± 17% and 44 ± 18% for omeprazole RP, and 6 ± 6% and 5 ± 5% for placebo. Both omeprazole formulations significantly increased intragastric pH compared with famotidine and placebo, but omeprazole tablet and RP was not significantly different from each other., Conclusion: Oral omeprazole tablet and RP provide superior gastric acid suppression to famotidine, and should therefore be considered more effective for the treatment of acid related disorders in dogs., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established., Objectives: To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach., Methods: Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i.d.) throughout the study. Intragastric pH was measured continuously for 72 h just inside the lower oesophageal sphincter (proximal stomach) and via a pH probe in the gastric cannula (ventral stomach)., Results: Neither proximal nor ventral 24 h gastric pH changed significantly between the 3 environmental situations. Mean hourly proximal gastric pH decreased significantly in the interval from 01.00-09.00 h compared to the interval from 13.00-20.00 h, regardless of environmental situation. Median hourly proximal pH only differed in the interval from 06.00-07.00 h compared to the interval 14.00-19.00 h. Neither mean nor median hourly ventral gastric pH varied significantly with the time of day., Conclusions: The change in housing status used in the current study did not affect acid exposure within either region of the equine stomach. The pH in the ventral stomach was uniformly stable throughout the study, while the proximal pH demonstrated a 24 h circadian pattern.

Reason for Performing Study: Administration of omeprazole paste per os to healthy neonatal foals has been shown to effectively increase intragastric pH, but has not been evaluated in sick neonatal foals., Objectives: To determine the effect of orally administered omeprazole paste on intragastric pH in clinically ill neonatal foals requiring nasogastric intubation., Methods: Intragastric pH was measured continuously for 24 h using an indwelling electrode and continuous data recording system in hospitalised neonatal foals age < or =2 days. Intragastric pH was measured for 12 h prior to (pretreatment period) and 12 h following (post treatment period) treatment with omeprazole paste (4 mg/kg bwt per os). All foals displayed periods of acidity (pH <4) prior to treatment. Statistical analysis compared pre- and post treatment mean and median intragastric pH, and percentage of time below pH 4., Results: Eight foals were evaluated age 1-3 days, a gestational age of at least 320 days or reported to be full term. The mean (3.19 +/- 1.50 vs. 6.20 +/- 0.93) and median (4.6 +/- 1.7 vs. 6.86 +/- 0.89) pH were significantly higher and the percentage of time below pH 4 (32.25 vs. 1.1%) was significantly lower in the post treatment compared to the pretreatment period., Conclusion: Omeprazole paste effectively increases intragastric pH in clinically ill neonatal foals after one dose at 4 mg/kg bwt orally.

The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Omeprazole (0.5 mg/kg, IV) was administered once daily for 5 days to 6 adult horses with gastric ulcers. Gastric juice was aspirated through the biopsy channel of an endoscope and pH was measured before and 1 hour after administration of omeprazole on day 1, and then before and after administration of omeprazole on day 5. Gastric ulcer scores were recorded on day 1 before administration of omeprazole and on day 5, 23 hours after the 4th daily dose. Gastric juice pH and ulcer scores were compared between the times. When compared with the pre-injection value (2.01 +/- 0.42), mean +/- SD gastric juice pH was significantly higher when measured 1 hour after administration of the initial dose (4.35 +/- 2.31), and before (5.27 +/- 1.74) and 1 hour after (7.00 +/- 0.25) administration of omeprazole on day 5. Nonglandular gastric ulcer number score significantly decreased from a mean +/- SD of 3.2 +/- 0.80 to 2.0 +/- 1.1, but nonglandular gastric ulcer severity score remained the same. Few glandular ulcers were seen in the study, and scores did not change. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste. Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment.

Reasons for Performing Study: Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible., Objective: To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals., Methods: Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography., Results: Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration., Conclusions: Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH., Potential Relevance: The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.

Objective: To evaluate the efficacy of omeprazole paste, a commonly used antiulcer drug, on intragastric pH in clinically normal neonatal foals., Animals: 6 clinically normal foals between 5 and 14 days of age., Procedure: Intragastric pH was recorded in each foal by use of a disposable antimony pH electrode with internal reference. Values for intragastric pH were recorded every 4 seconds by use of an ambulatory pH monitor. There were two 24-hour recordings of intragastric pH for each foal, with 24 hours between recordings. Foals were not administered any drugs during the first recording. Foals were administered omeprazole paste (4 mg/kg, PO) 1 hour after the start of the second recording. Mean pH was calculated for each hour of each 24-hour recording session. Hourly mean values were compared between the first and second 24-hour recordings., Results: Complete data were obtained from 4 of 6 foals during the first 24-hour recording and 6 of 6 foals during the second 24-hour recording. Foals had significantly higher mean hourly intragastric pH for hours 2 to 22 following omeprazole administration, compared with corresponding hourly pH values in foals during the first recording., Conclusion and Clinical Relevance: Omeprazole paste can effectively increase intragastric pH in clinically normal neonatal foals within 2 hours after oral administration of the first dose and can be administered to neonatal foals at the rate of 4 mg/kg, PO, every 24 hours.

Objective: To characterize intragastric pH profiles in critically ill foals and determine whether administration of ranitidine altered pH profiles., Design: Prospective observational study., Animals: 23 hospitalized neonatal foals < or = 4 days of age., Procedure: Intragastric pH was measured continuously for up to 24 hours by use of an indwelling electrode and continuous data recording system. In 21 foals, ranitidine was administered IV., Results: 10 foals had predominantly or exclusively alkaline profiles, 10 had profiles typical of those reported for healthy foals, with periods of acidity (hourly mean pH < 5.0 at least once), and 3 had atypical profiles with periods of acidity. All 10 foals that had intragastric pH profiles typical of healthy foals survived, whereas only 2 foals with alkaline profiles survived, and none of the foals with atypical profiles survived. The effects of ranitidine administration could not be assessed in 13 foals because of a high baseline intragastric pH. In 7 of the remaining 9, ranitidine administration resulted in an alkalinizing response, but this response was often of blunted duration. Ranitidine administration did not appear to alter the intragastric pH profile in the remaining 2 foals., Conclusions and Clinical Relevance: Results suggested that hospitalized critically ill foals often have intragastric pH profiles different from those reported for healthy foals and may respond differently to ranitidine administration than do healthy foals. Many critically ill foals have continuously alkaline intragastric pH profiles, questioning the need for prophylactic administration of ranitidine in all critically ill foals.

Objectives: To determine the effects of orally administered omeprazole, as enteric-coated capsules, on baseline and stimulated gastric acid secretion in horses., Animals: 5 healthy 8-year-old mixed-breed horses fitted with gastric cannulas., Procedure: Enteric-coated granules of omeprazole were mixed with corn syrup and administered orally once daily for 5 consecutive days. On days 1 and 5 beginning 5 hours after omeprazole administration, 4 gastric fluid samples were collected, each for 15 minutes, via the gastric cannula (baseline samples). Pentagastrin was administered IV as a constant infusion for the subsequent 2 hours, and 15-minute gastric fluid samples were again collected (stimulated samples). Fluid volume, acidity (mmol H-/L), and pH and gastric acid production (mmol H+) were determined for all baseline samples and for stimulated samples collected during the second hour of pentagastrin infusion. Control experiments were done in a similar manner after giving corn syrup alone to the same horses., Results: Compared with values obtained during control experiments, baseline and stimulated gastric fluid acidity and gastric acid production significantly decreased, and the mean pH of gastric fluid samples significantly increased, after horses were given 5 daily doses of omeprazole., Conclusions and Clinical Relevance: Enteric-coated omeprazole (1.0 mg/kg of body weight; PO) administered once daily for 5 days significantly inhibited unstimulated and pentagastrin-stimulated gastric acid secretion in horses. This commercially available formulation of omeprazole may be efficacious in the treatment of gastroduodenal ulcers in horses.

Objective: To determine intragastric pH in newborn foals and to examine the effect of i.v. or oral administration of an H2-receptor antagonist on intragastric pH., Design: Prospective controlled study., Animals: 6 healthy mixed-breed neonatal foals., Procedure: Intragastric pH was measured, using an antimony electrode. Foals were monitored on days 2, 4, and 6 after birth, and each received 3 treatments. The pH was recorded for 4 hours before treatment and for 10 hours after ranitidine administration (2 mg/kg [0.91 mg/lb] of body weight, i.v.; 6.6 mg/kg [3 mg/lb], PO) or 20 hours after corn syrup administration. Mean and median pH and percentage of time pH was > or = 4 were calculated., Results: Mean intragastric pH significantly increased for 5 hours after i.v. administration of ranitidine, compared with baseline data. Percentage of time intragastric pH was > or = 4 increased significantly for 4 hours after ranitidine administration, and median pH increased significantly for hours 2 to 4 after administration. Oral administration of ranitidine significantly increased mean and median pH for hours 2 to 8 after administration and percentage of time pH was > or = 4 for hours 2 to 7 after administration., Clinical Implications: Neonatal foals have highly acidic gastric fluid. Intravenous or oral administration of ranitidine significantly increased intragastric pH for 4 and 8 hours, respectively. Suckling affected intragastric pH and underscored the need for frequent feeding of neonatal foals.

Objective: To assess the effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in clinically normal horses and to develop guidelines on the use of these agents for treatment of peptic ulcer disease in horses., Design: Prospective, randomized, controlled trial., Animals: 5 clinically normal adult horses with chronically implanted gastric cannulas., Procedure: Each horse received all 5 treatments (30 g of aluminum hydroxide/15 g of magnesium hydroxide, 12 g of aluminum hydroxide/6 g of magnesium hydroxide, 10.5 g of bismuth subsalicylate, 26.25 g of bismuth subsalicylate, and 5% methylcellulose control) with only 1 experiment performed each day. Gastric pH was measured via a glass electrode inserted through the gastric cannula for 1 hour before treatment and continued for 2 hours after treatment. Food or water was not given to the horses during the experiment. Measurements of gastric pH obtained during posttreatment hours were compared with pretreatment gastric pH values., Results: Only a dose of 30 g of aluminum hydroxide/ 15 g of magnesium hydroxide resulted in a significant increase in gastric pH over baseline or control values. Mean pH was 5.2 +/- 0.62 and 4.59 +/- 0.48 for posttreatment hours 1 and 2, respectively., Clinical Implications: Oral administration of 30 g of aluminum hydroxide/15 g of magnesium hydroxide to adult horses should result in a mean hourly gastric pH > or = 4.0 for at least 2 hours.

We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administration. In the presence of acid-suppressant treatment, plasma gastrin concentration correlated significantly with gastric pH (Spearman's rank correlation coefficient, rho = 0.445, P < 0.01), whereas basal pH and plasma gastrin concentration were not correlated. The effect was not great, and a dose-dependency was not found. Intravenously administered omeprazole was subject to two-compartment pharmacokinetics, and there was evidence for saturable steps in the redistribution and elimination phases. Dosage of 0.25 mg/kg induced approximately half-maximal inhibition of basal gastric pH in these ponies and was associated with area under the concentration vs time curve of 0.7 mumol.h/L, which corresponds reasonably with results of other species. Omeprazole may represent a useful alternative acid-suppressant agent in horses, but further work is required to relate the dose-dependent effects found in this study to well-defined targets of acid suppression in clinical cases.

Intragastric pH monitoring was investigated in ponies. In cadaver stomachs, close contact with the mucosa led to high pH readings if nonweighted electrodes were used. However, pH recorded by weighted electrodes was markedly less affected by mucosal contact (P < 0.001). The latter were used for subsequent trials. In vivo, high correlations were found between pH recorded by weighted electrodes with or without a wire guard to prevent mucosal contact (correlation, r = 0.866; P < 0.001). Readings from each correlated well with those from simultaneous gastric aspirates (r = 0.774 and r = 0.807, respectively; P < 0.001 for both correlations). Plain electrodes recorded more highly variable (temporally heterogeneous) pH than did guarded electrodes. In vitro, trials using equine gastric fluid indicated that this resulted from greater responsiveness of the plain electrode. In vivo, episodes of nearly neutral pH were a common feature, and high pH correlated with intensely yellow-green, neutral fluid in the stomach (rank correlation, rho = 0.626; P < 0.01). Concentration of bile acids did not correlate with pH or color score (rho = -0.158 and rho = 0.076, respectively). Causes of the episodes could include salivary influx, duodenogastric reflux, and variable gastric acid secretion. Pentagastrin infusion (0.6 microgram/kg of body weight/h) reduced intragastric pH (P = 0.018), but episodes of neutrality still occurred. Experiments in fed ponies indicated possible existence of a stable pH gradient, from neutral dorsally to heterogeneous and more acidic ventrally. Care was required in the rational choice of summary variables for expression of monitored pH data. Of the frequency distributions of 3 summary variables assessed in this study (mean, median, and percentage of data > pH 4), only that of the mean approached normality. Thus, use of the mean may allow analysis by parametric statistical methods. Intragastric pH monitoring was found to be a useful technique. Episodes of increased pH were often identified. These may represent episodic duodenogastric reflux.

A glass combined pH-reference electrode was placed in the stomachs of 5 adult horses and pH was recorded every 6 mins for 24 h while (1) feed and all bedding materials were withheld for 24 h (unfed), (2) horses had free access to Timothy grass hay for 24 h (fed), and (3) horses had free access to Timothy grass hay and were treated with ranitidine, 6.6 mg/kg body weight, orally, every 8 h for 48 h (fed + ranitidine). There was a significant (P = 0.007) difference in median 24-h gastric pH amongst the 3 protocols, the value being 3.1 in fed horses and 1.55 in unfed horses (P = 0.05) and 4.6 in fed + ranitidine horses (P = 0.05 compared with fed horses). The percentage of pH readings < 2.0 was significantly greater (P = 0.05) in unfed (76%) than in fed (30%) horses, and in fed horses than in fed + ranitidine (9%) horses. The percentage of readings > 2.0, 3.0, 4.0, 5.0 and 6.0 were each significantly (P = 0.05) greater in fed + ranitidine horses than in fed horses, and in fed than in unfed horses. There was no difference (P = 0.13) between median gastric pH values from different times of day in unfed horses (00:00 to 06:00 h, 1.5; 06:00 to 12:00 h, 1.6; 12:00 to 18:00 h, 1.7; and 18:00 to 24:00 h, 1.5). We conclude that gastric acidity is greatest when horses do not have access to feed material and that ranitidine effectively suppresses gastric acidity in horses under conditions of free access to hay.

Gastric pH varied widely among eight fasted ponies, of which seven exhibited discrete episodes of spontaneous alkalinisation (SA). SA occurred at all times of the study and no significant variation in the summary variables of pH (median pH, mean pH and percentage of readings exceeding pH 4.0) was noted among the periods 0 to eight, eight to 16 and 16 to 24 hours. The occurrence of SA has significant implications for the performance of acid secretory studies in the fasted pony. There was, however, no significant correlation between pH and plasma gastrin concentration measured using a commercially available radioimmunoassay kit validated for use in the horse. This implies a lack of dependency of the incidence of SA on plasma gastrin or, conversely, of plasma gastrin on the variable pH associated with SA.

Gastric pH was monitored in neonatal foals from birth to 3 months of age. Background pH decreased, especially during the first week of life. Milk had complex effects that depended on pH prior to sucking, confounded by the age of the foal: nearly neutral background pH tended to be acidified after milk intake; moderately acid background pH tended to be neutralized; low background pH was only slightly increased by milk. Absolute magnitude of the effects of milk decreased with age. Existence of a proulcerative intragastric environment in preweaning foals is postulated, but this must be considered in the context of what probably is a multifactorial pathogenesis.

A Tigon fistula was surgically implanted into the third compartment of the stomach of 5 llamas to allow measurement of gastric pH. The llamas were allotted into 2 groups and given flunixin meglumine or cimetidine hydrochloride for 3 days. After 4 days without treatment, the drugs given to each group were reversed. Measurements of gastric pH were taken every 30 minutes for 6 hours, using an automated pH meter. The pH measurements after drug administration were compared with measurements obtained during a pretreatment control period. Gastric pH during pretreatment control periods had a mean of 1.43 +/- 0.063 (mean +/- SE). The use of flunixin did not significantly decrease gastric pH, compared with pretreatment controls. Gastric pH was significantly higher within the first 30 minutes after administering cimetidine, compared with pretreatment controls, but this difference disappeared at all later times.

The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently < 2.7. Administration of octreotide at these same dosages induced gastric pH values > 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respectively. Treatment at all dosages increased the pH of gastric fluid, compared with control values. The duration of the increase in pH was significantly (P < 0.05) different than that of the control treatment, even for the lowest dosage, 0.1 microgram/kg.

Crossbred pigs (n = 144, average age and weight = 28 +/- 3 d, 7.5 kg) were used in two 6-wk trials to assess the effects of dietary pH and P source on growth performance, gastrointestinal digesta pH and chloride ion concentration (Cl-), and bone characteristics. Treatments were randomly allotted within blocks (based on weight within gender) to a 3 x 2 factorial arrangement with three dietary pH levels (5.4, 6.0, and 6.7) and two P sources: dicalcium phosphate (DCP) and defluorinated phosphate (DFP). Pigs fed the pH 6.7 diet had reduced ADG (P less than .01) and average daily feed intakes (ADFI; P less than .001) during wk 1 to 3 and overall compared with pigs fed the pH 6.0 diet, but ADG and ADFI were not affected when the pH 5.4 diet was fed. There was a dietary pH x P source interaction (P less than .05) for ADFI. Pigs had decreased ADFI as dietary pH was increased from 6.0 to 6.7 for both DCP and DFP, but ADFI was similar for the pH 6.0 and 5.4 diets with DFP, whereas ADFI was greater for the pH 5.4 diet with DCP. Dietary pH did not influence ADFI:ADG ratio (F:G; P greater than .05), and P source had no effect (P greater than .05) on either ADG, ADFI, or F:G.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of intramuscular administration of multiple doses of cimetidine and ranitidine on basal gastric pH, free and total acid content from young adult pigs were studied. Cimetidine (4.5 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a simultaneous reduction in free acid content at two, three and 26 hours after the administration of the eighth dose. Ranitidine (0.75 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a concomitant reduction in free acid content at three and 38 hours after the administration of the eight dose. Neither cimetidine nor ranitidine had any significant effects on total acid content. These results confirm that the pig is a basal acid secretor and that the pharmacodynamics and pharmacokinetics of cimetidine and ranitidine in pigs might be different from those in humans.

A chronically indwelling gastric fistula was implanted into rats. To collect gastric acid, a collection system was coupled to the fistula. This system operated by infusing physiological saline directly into the stomach of unanesthetized rats; the acid content of the perfusate was immediately determined by automatic titration machinery. Using this technique, a value of 3.25 uEq H+/2 minutes was obtained as the basal gastric secretion. For a sham-fed test meal of 2 ml of 36% sucrose, the stimulated phase of gastric acid secretion consisted of a dynamic response (peak 200% of basal) with a brief latency (< 2 minutes) and short duration (< 24 minutes). Results indicated that this response to sham feeding was a cephalic response, since direct infusion of a similar test meal into the stomach did not alter basal gastric acid output. Experience with the perfusion-collection technique indicated that the procedure was a sensitive nondisruptive method for chronic gastric acid collection from unanesthetized animals.

The basal gastric pH and free acid contents from five young adult healthy horses were determined at one hour intervals for eight hours. The basal gastric pH and free acid contents varied from 1.63 +/- 0.06 to 1.97 +/- 0.11 and 26.42 +/- 4.14 to 17.92 +/- 5.28 mmol litre-1, respectively. Misoprostol, a methylester analogue of prostaglandin (5 micrograms kg-1, orally) produced a time-dependent increase in the basal gastric pH to above 3.5 (P less than 0.05) at three, four and five hours after administration with a concomitant reduction of 80 to 90 per cent in the basal gastric free acid contents throughout the eight hour period monitored. Omeprazole, a benzimidazole derivative (0.5 mg kg-1, intravenously) increased the basal gastric pH to above 3.5 at two and three hours after administration with a concomitant reduction of 65 to 90 per cent in the basal gastric free acid contents for seven of the eight hour periods monitored. These results confirm that the horse is a basal acid secretor, and both misoprostol and omeprazole are effective inhibitors of the basal gastric acid secretion, thus establishing that both prostaglandins and H+/K+-ATPase play an important role in controlling parietal cell function of the equine gastric mucosa.

The basal gastric pH, free and total acid contents from five adult horses were determined at two-hour intervals for six- to eight-hour periods. The basal gastric pH, free and total acid contents varied from 2.14 +/- 0.08 to 2.41 +/- 0.14, 28.63 +/- 8.27 to 17.89 +/- 2.86 mmol litre-1 and 41.38 +/- 9.72 to 37.38 +/- 3.70 mmol litre-1, respectively. Cimetidine (8.8 mg kg-1 orally) and ranitidine (2.2 mg kg-1 orally) increased the basal gastric pH to above 3.6 (P less than 0.05) with a concomitant reduction of 75 per cent and 75 to 100 per cent in the basal gastric free acid content, respectively, for an eight-hour period. Cimetidine (4.4 mg kg-1, intramuscularly) and ranitidine (1.4 mg kg-1, intramuscularly) increased the basal gastric pH to above 3.6 with a concomitant reduction of 54 to 93 per cent and 69 to 100 per cent in the basal gastric free acid content, respectively, for an eight-hour period. This study shows that the horse is a basal acid secretor, and that cimetidine and ranitidine, two widely used histaminergic-H2 type antagonists in human clinical practice are effective in horses with ranitidine being approximately four times more potent than cimetidine.

The effect of gizzerosine [2-amino-9-(4-imidazolyl)-7-azanonanoic acid], which causes gizzard erosion in chicks, on gastric acid secretion was studied in young chicks. Three-day-old broiler chicks given a diet containing synthetic DL-gizzerosine showed severe symptoms of gizzard erosion after 7 days. The pH of the gastric and duodenal contents of these chicks was lower than that of the control chicks, demonstrating that acid secretion was enhanced in gizzerosine-fed chicks. The pH of gastric contents was lower and the amount of total gastric acid was higher in 1-day fasted chicks injected with gizzerosine intravenously than in those injected with physiological saline solution. The intramuscular injection of cimetidine, H2-receptor antagonist of histamine, blocked the stimulation of acid secretion by gizzerosine and by histamine. Cimetidine added in feed also prevented gizzard erosion, which was induced by feeding overheated mackerel meal. The results showed that gizzard erosion developed after oral or intravenous administration of gizzerosine is caused at least in part by the enhanced gastric acid secretion. Furthermore, it was suggested that gizzerosine acts on H2-receptor of histamine and stimulates the gastric acid secretion in broiler chicks.