RESUMO
Introduction: Development 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. Methods: Pantoprazole 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. Results: Following 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. Discussion: The 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.
RESUMO
Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.
