Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Fladung, Rachel; Smith, Joe S.; Hines, Melissa T.; Soto-Gonzalez, Windy; Fayne, Bryanna; Rahn, Rebecca R.; Escher, Olivia G.; Harvill, Lainey; Bergman, Joan; Garcia, Jessica; Kreuder, Amanda J.; Cox, Sherry

doi:10.3389/fvets.2022.968973

Cited by 8 publications

(10 citation statements)

References 22 publications

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“…While uncommon, a bioavailability of >100% can occur for several reasons, such as distribution between compartments, or as a result of sampling schedule. A bioavailability of >100% has been observed for pantoprazole in alpacas (115%) ( 14 ), as well as a similar proton pump inhibitor esomeprazole in goats ( F = 116%) ( 32 ). This could indicate non-linear pharmacokinetics at higher dosages or potentially flip flop pharmacokinetics, although flip flop pharmacokinetics seems less likely comparing the slopes of each route.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, while pH timepoints were collected at 18 hours, these were not presented, as it appears that additional sampling of pH after the second milk feeding should be considered for future studies in calves to truly account for pH changes from pantoprazole, vs. the second milk feeding. This model of cannulation for abomasal fluid sampling could be utilized for other gastroprotectant therapies in ruminants, such as esomeprazole, the S-enantiomer of omeprazole ( 32 ). Future studies could also evaluate the variation within individuals of a population to see if factors such as disease status or genetic polymorphism influence the metabolism of pantoprazole.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves

et al. 2023

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“…If ulcers are suspected, treatment with a proton pump inhibitor, such as pantoprazole or esomeprazole can be considered. [3][4][5] Pantoprazole by injection 0.5 mg/lb IV; 0.5 to 1 mg/lb SC, q 24 hr, x 3 days, has been demonstrated to reduce abomasal acid secretion in alpacas, and calves. 6,7 The author has unpublished data supporting pantoprazole and esomeprazole use in sheep and goats as well.…”

Section: Pain Managementmentioning

confidence: 99%

Small ruminant drug use for the cow vet

Smith

2023

AABP Proceedings

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With the rapid increase in numbers and popularity of small ruminants in North America, there is a need for ambulatory practitioners to provide for their care. With the economics of small ruminant practice not being near those of bovine practice, combined with extremely limited drugs for sheep and goats, there is an opportunity for creative solutions regarding bovine therapies for caprine and ovine patients. In this review the role of the small ruminant as a food animal will be discussed along with extralabel drug usage for food animal species. Analgesic drugs will be discussed for utility in ambulatory practice settings. Use of approved and extralabel antimicrobials will be investigated for control and prevention of infectious disease. Sedation practices will be mentioned, along with additional resources to guide the bovine veterinarian with small ruminant treatment decisions.

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“…No drugs had been administered to the sheep for 18 days prior to the study. Esomeprazole (Esomeprazole Sodium for injection, Mylan International, Rockford Il) was administered at a 1.0 mg/kg dosage as a single dose (based on a described intravenous dose for goats) (12), with the dosing catheter flushed with 10 mL of 0.9% saline afterwards to ensure all drug was administered.…”

Section: Animalsmentioning

confidence: 99%

“…Esomeprazole and its metabolite concentrations were detected in sheep samples using a validated method for proton pump inhibitors in goats (12,13). The system consisted of a 2695 separations module and a 2487 UV absorbance detector (Waters, Milford, MA, United States).…”

Section: High Performance Liquid Chromatography Analysismentioning

confidence: 99%

The pharmacokinetics and pharmacodynamics of esomeprazole in sheep after intravenous dosing

et al. 2023

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Abomasal (gastric) ulceration is a morbidity in sheep, and currently, there is a paucity of pharmacokinetic and pharmacodynamic data for gastroprotectant drugs reported for this species. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via increasing the gastric pH. The objective of this study was to report the pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single intravenous dosing. Four healthy adult Southdown cross ewes had blood collected over a 24 h time period after single intravenous dosing of esomeprazole at 1.0 mg/kg. Abomasal fluid was sampled over 24 h before and after esomeprazole administration. Plasma samples were analyzed for concentrations of esomeprazole and the esomeprazole metabolite, esomeprazole sulfone by high performance liquid chromatography. Pharmacokinetic and pharmacodynamic data were evaluated with specialized software. Esomeprazole was rapidly eliminated after IV administration. Elimination half-life, area under the curve, initial concentration (C0), and clearance were 0.2 h, 1,197 h*ng/mL, 4,321 ng/mL, and 0.83 mL/h/kg, respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16 h, 22.5 h*ng/mL, and 65.0 ng/mL, respectively. Abomasal pH was significantly elevated from 1 to 6 h after administration and remained above 4.0 for at least 8 h after administration. No adverse effects were noted in these sheep. 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.

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Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Cited by 8 publications

References 22 publications

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves

Small ruminant drug use for the cow vet

The pharmacokinetics and pharmacodynamics of esomeprazole in sheep after intravenous dosing

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