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

PLoS One. 2024 Jun 12;19(6):e0304533. doi: 10.1371/journal.pone.0304533. eCollection 2024.

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.

MeSH terms

  • Abomasum / drug effects
  • Administration, Intravenous
  • Animals
  • Cross-Over Studies
  • Female
  • Hydrogen-Ion Concentration
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Pantoprazole* / administration & dosage
  • Pantoprazole* / pharmacokinetics
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / pharmacokinetics
  • Proton Pump Inhibitors / pharmacology
  • Sheep

Substances

  • Pantoprazole
  • Proton Pump Inhibitors

Grants and funding

The UTKCVM LACS Department Startup, UTKCVM COE program, and LMU Summer Research Assistant Program supported part of this work.