EFFICACY OF GASTRIC ACID-LOWERING THERAPY IN THE DOG

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Abstract

Introduction: Gastric acid suppression is a recommended therapy for gastric ulceration. Human studies suggest that optimal healing of duodenal ulcers occurs at gastric pH >3 for 75% of the day. The objective of this study was to evaluate the efficacy of 4 gastric acid suppressants at recommended veterinary doses. Drug effect was based on the 24-hour median pH and the percentage of time that the intragastric pH ≥3 in a 24 hour period.

Methods: The study was conducted in 12 healthy Beagle dogs and was a double-blind, randomized, multiple cross-over comparison of a placebo (saline IV q12 h), ranitidine 2 mg/kg IV q12 h, famotidine 0.5 mg/kg IV q12 h, pantoprazole 1 mg/kg IV q24 h, and omeprazole (unblinded) ∼1 mg/kg PO q24 h. Continuous 24-hour intragastric pH measurements were obtained via PEG tube. Prior to drug testing, 24-hour pH measurements were recorded in fasted and fed dogs. Thereafter, dogs were fed standardized meals throughout the remainder of the study period. Drugs were administered for 1 week with a one-week washout period between tests. Data were obtained on Day 0 (baseline), Day 2 and Day 6 of treatment. Following the randomized study, famotidine 0.5 mg/kg IV q8 h and omeprazole ∼1 mg/kg + bicarbonate q12 h via PEG tube were evaluated in 6 dogs, respectively. Appropriate statistical analyses were applied to calculate the 24-hour median pH and percentage of time that the test drug maintained intragastric pH≥3 over 24 hours.

Results: The 24-hour median pH of fasted dogs was 4.44 vs. fed dogs 1.30 (p<0.0001). The % time pH≥3: fasted dogs 66.0% vs. fed dogs 13.3% (p<0.0001). The 24-hour median pH was (bold denotes significance when compared to saline) - saline pH 1.81, ranitidine Day 2–pH 2.53, Day 6–pH 2.05, famotidine Day 2–pH 2.83, Day 6–pH 3.68, pantoprazole Day 2–pH 3.11, Day 6–pH 3.49, omeprazole Day 2–pH 3.86, Day 6–pH 4.09. The % time pH≥3: saline 32.9%; ranitidine day 2 – 44.6%, Day 6 – 37.2%; famotidine: Day 2 – 48.9%, Day 6 – 60.1%; pantoprazole: Day 2 – 54.2%, Day 6 – 59.1%; omeprazole: Day 2 – 66.9%, Day 6 – 70.2%. The 24-hour median pH of omeprazole + bicarbonate q12 h was 4.7 on Day 2 and 4.9 on Day 6; the % time pH ≥3 was 90.9% on Day 2 and 78.4% on Day 6, respectively. No significant difference was noted in any parameter comparing famotidine q8 h and q12 h.

Conclusions: Fasted dogs had a significantly higher pH than fed dogs. Omeprazole was the only drug tested that approached the potential therapeutic efficacy for healing of duodenal ulcers when assessed by criteria for human patients. Variation existed amongst dogs in all drugs tested.

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