Abstract: Background: Abomasal ulceration presents a morbidity in sheep, and currently there is a lack of pharmacokinetic and pharmacodynamic data for proton pump inhibitors reported for use in sheep. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via decreasing acid secretion.
Objective: To report pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single dosing (1.0 mg/kg, intravenous).
Animals: Four healthy adult ewes.
Methods: Blood samples were collected at fifteen time points over a twenty-four hour period after intravenous dosing. Samples were analyzed for concentrations of esomeprazole and the metabolite esomeprazole sulfone by high performance liquid chromatography. Abomasal fluid was sampled ten times over twenty-four hours before and after drug administration. Pharmacokinetic and pharmacodynamic data were evaluated with commercial software.
Results: Esomeprazole was rapidly eliminated. Elimination half-life, area under the curve, initial concentration and clearance were 0.2 hr, 1197 hr*ng/mL, 4321 ng/mL, and 0.83 mL/hr/kg respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16 hr, 22.5 hr*ng/mL, and 65.0 ng/mL respectively. Abomasal pH was significantly elevated from 1-6 hr after administration, and remained above 4 for at least 8 hours after administration. No adverse effects were noted in the study ewes.
Conclusions: Esomeprazole was rapidly eliminated in sheep, similar to goats. Abomasal pH was increased, but future studies will be necessary to develop a clinical management approach to the use of esomeprazole in sheep.
Learning Objectives:
Understand the study design for this investigation of the pharmacokinatics and pharmacodynamics of esomeprazole in sheep
Understand the pharmacokinetics of esomeprazole in sheep after a single intravenous dose
Utilize the pharmacodynamic findings of this study for gastroprotection in sheep
