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

Abstract

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.

ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats

“…Standard doses of esomeprazole, the S‐enantiomer of omeprazole, resulted in greater gastric acid control compared to standard doses of traditional PPIs . The pharmacokinetics and acid suppressant efficacy of esomeprazole after IV, PO, and SQ administration in healthy beagles has been studied, but it was not compared to other PPIs . Intravenously administered esomeprazole was documented to significantly increase gastric and esophageal pH in dogs undergoing elective orthopedic procedures .…”

Comparative analysis of the effect of IV administered acid suppressants on gastric pH in dogs

“…Although additional study is needed in dogs with upper GI bleeding, our findings lead us to believe that esomeprazole and famotidine CRI provide superior gastric acid suppression compared to pantoprazole. In previous studies, both parenterally and PO administered esomeprazole formulations have proven to provide potent acid suppression in dogs . And, in a recent report, a lower dose of IV administered esomeprazole (0.5 mg/kg q 12 hours) was still effective in raising gastric pH in dogs compared to 1.0 mg/kg q12h .…”

“…In previous studies, both parenterally and PO administered esomeprazole formulations have proven to provide potent acid suppression in dogs. 10 And, in a recent report, a lower dose of IV administered esomeprazole (0.5 mg/kg q 12 hours) was still effective in raising gastric pH in dogs compared to 1.0 mg/kg q12h. 16 Orally administered esomeprazole was superior to other PO administered FDAapproved PPIs in mucosal erosion healing and heartburn relief in people.…”

“…18 A diminished acid suppressing effect can be observed with PO administered famotidine over time in dogs, 13 but we cannot comment as to whether this occurs after an IV administered CRI of famotidine as can occur in people with IV administered ranitidine. 19 In a previous study 10 and in the current study, a diminished efficacy over time was not observed; however, medications were only administered for 72 hours. Moreover, in the current study, only 3 dogs receiving famotidine CRI had a capsule in place at the end of the 72-hour monitoring period.…”

“…Esomeprazole might provide superior acid suppression compared to other PPIs . Esomeprazole dramatically increases gastric pH in dogs, but a comparative analysis with other gastric acid suppressants is not available. A constant rate infusion (CRI) of famotidine at a higher total daily dose also provides potent acid suppression in healthy dogs .…”