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Pharmacodynamics of 2 dosages of orally administered esomeprazole in client-owned, healthy dogs: A prospective,
Abby Ostronic1, Christine Gremillion2, Song Zhang3
1Texas A&M University, Department of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Background:
Esomeprazole use is increasing in dogs, but the gastrointestinal adverse events associated with q12h dosing necessitate pharmacodynamic evaluation of a reduced dose and frequency of administration.
Objectives:
To compare the efficacy of 2 doses of (q24h) esomeprazole in raising intragastric pH in dogs.
Animals:
Nine healthy, client-owned dogs, >20 kg.
Methods:
Prospective, randomized, double blinded, crossover study. Esomeprazole (0.5 or 1 mg/kg q24h) was orally administered for up to 5 days per treatment arm, and the mean percentage time intragastric pH was ≥3 (MPT3) and ≥4 (MPT4) for 24 hours periods were compared to pretreatment pH using a continuous pH monitoring system. Dogs failing to reach pH goals (MPT3 ≥75%, MPT4 ≥66%) with once daily dosing received esomeprazole 1 mg/kg PO q12h to determine if a higher dose would improve acid suppression.
Results:
No significant difference in the MPT3 or MPT4 was identified between treatments for any time point (P > .05). Both doses increased the MPT pH ≥3 and 4 median [range] (0.5 mg/kg, 1 mg/kg) on days 1 (MPT3: 76.8% [44-100], 69.2% [28.2-100]; MPT4: 65.6% [16.7-99.3], 54.9% [14.9-93.3]; P = .0009) and 2 (MPT3:77.2% [27.4-100], 75.4% [49.4-89.5]; MPT4: 66.3% [15.5-100], 59.7% [33.8-81.2]; P = .0005) of PPI treatment compared to pretreatment (MPT3: 58.3% [0.02-93.9], 52.6% [6.1-94.7]; MPT4: 25.2% [0-86.8], 32.4% [1.8-89.3]). Six dogs (66%, [0.36, 0.97]) reached pH goals established in humans with q24h dosing.
Conclusions And Clinical Importance:
Both q24h PO esomeprazole doses were effective in raising intragastric pH, despite high intersubject variability, but 33% of dogs required q12h dosing to reach pH goals.
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