The effects of dose and diet on the pharmacodynamics of esomeprazole in the horse

Background: Esomeprazole warrants further investigation as a treatment for equine gastric ulcer syndrome. Objectives: To investigate the duration of intraday acid suppression achieved with two doses of esomeprazole under two dietary conditions. Study design: A four way crossover design. Methods: Six adult Thoroughbreds instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00–07.00 h) for 6 consecutive days (Days 0–5). Baseline data was recorded on Day 0 and esomeprazole was administered on Days 1–5. Two doses (0.5 and 2.0 mg/kg bwt/day per os once daily) and two diets (a high grain/low fibre (HG/LF) and ad libitum hay (HAY) diet) were studied. Data for the percentage of time pH was above 4 (%tpH>4) and median intraday pH was reported for two measurement points and analysed using generalised estimating equations. Results: An inconsistent effect of both diet and dose was evident with mean %tpH>4 and mean of the median intraday pHs typically higher at the 2.0 mg/kg bwt dose and in HG/LF diet. A cumulative effect of dosing was present with the magnitude of acid suppression observed on Day 5 consistently higher than that observed on Day 1. The magnitude of acid suppression, at measurement point 1, compared favourably with previous reports on omeprazole and exceeded human therapeutic breakpoints for the 0.5 mg/kg bwt dose in the HG/LF diet and 2.0 mg/kg bwt dose in the HAY diet. Main limitations: Instrumentation may have modified gastric function and horses were not fasted or exercised. Conclusions: The findings of the present study suggested that both dose and diet affect the response to esomeprazole in the horse and that a cumulative effect is present over the first 5 days of treatment. Further investigation into the clinical efficacy of esomeprazole and trials directly comparing esomeprazole and omeprazole appear to be warranted