Pharmacokinetics and pharmacodynamics of intravenously and subcutaneously administered pantoprazole in sheep (Ovis aries)

Abstract

Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.

Fig 1. Abomasal pH of study ewes (n = 4) on day 0, as well as days 1–3 post pantoprazole (1 mg/kg) administration via the intravenous (IV: Orange) or subcutaneous (SC: Grey) routes.

Asterisk (*) indicates statistically significant (P < 0.05) difference from pre-pantoprazole administration baseline. Dashed line represents a pH of 4.0.

Fig 2. Time vs concentration curve for pantoprazole after intravenous (orange diamond) and subcutaneous (grey square) administration of 1.0 mg/kg to adult ewes.

Upward bars represent error.

Fig 3. Time vs concentration curve for pantoprazole sulfone after intravenous (orange diamond) and subcutaneous (grey square) administration of 1.0 mg/kg pantoprazole sodium to adult ewes.

Upward bars represent error.