Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves

Abstract

IntroductionDevelopment of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period.MethodsPantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer.ResultsFollowing Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3.DiscussionThe reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.

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

“…Four, open Southdown-cross ewes, aged 2.75 ± 0.96 years of age and weighing 67.9 ± 7.6 kg were utilized for this study. The ewes had an abomasal cannula implanted 2 weeks prior as previously described for calves and ewes [ 15 , 17 ]. Ewes were allowed to acclimate for one week upon arrival at the Veterinary Research and Education Center facility.…”

“…Abomasal fluid was collected via the abomasal cannula as described for calves and ewes [ 15 , 17 ]. Fluid was collected each day of the study [day 0: pre-pantoprazole administration “control” and day 1–3 post-pantoprazole administration (q 24 hr)] using the same schedule: 0, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h for both control samples as well as after esomeprazole administration.…”

“…As previously described for pantoprazole, pharmacokinetic analysis of total pantoprazole plasma concentrations was completed using a statistical moment (i.e., non-compartmental) approach in commercial software (PKanalix, Monolix Suite 2023R1, Lixoft, France) [ 14 , 15 ]. Time versus concentration figures for pantoprazole were produced using a commercial software program (GraphPad Prism version 8.0, GraphPad Software, La Jolla California USA).…”

“…Statistical evaluation of pH data was performed as reported by Olivarez et al [ 15 ]. First data from pH values were evaluated for normality.…”

“…However, the pharmacokinetics of pantoprazole are less well described with reports existing for alpacas, goats and calves [ 8 , 14 – 16 ]. Even less investigated is the pharmacodynamic effect of pantoprazole on abomasal pH, with descriptions in the literature only for alpacas and calves [ 8 , 15 ]. As such, the clinical usage of pantoprazole in sheep is currently lacking support in the form of pharmacodynamic evaluation of the effects on abomasal pH.…”