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静脉和皮下给予羊(Ovis aries)泮托拉唑的药代动力学和药效学。

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

机构信息

Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, United States of America.

Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States of America.

出版信息

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.

摘要

网胃溃疡在各个年龄段的绵羊中均有发现,但关于治疗干预的研究有限。质子泵抑制剂(PPIs)如泮托拉唑在临床上被广泛应用,但关于其在成年绵羊中的疗效证据不足。在成年绵羊中,静脉内和皮下给予 1.0mg/kg 的泮托拉唑可使胃内容物 pH 值升高,与给药前的基线相比。目的是评估单次和多次给药后泮托拉唑对成年绵羊胃内容物 pH 值的影响。第三个目的是描述 IV 和 SC 泮托拉唑的药代动力学参数。本研究采用随机、2 向交叉试验,选取 4 只先前在网胃内置入胃造口管的临床健康成年南方杜绵羊。绵羊接受单次和 3 剂量方案(每 24 小时一次)的泮托拉唑(1.0mg/kg)治疗。在 10 天洗脱期后,应用相反的治疗方案。连续 24 小时采集血液以分析泮托拉唑浓度,96 小时内每隔一段时间测量胃内容物 pH 值。在给药后 24 小时内,胃内容物 pH 值在泮托拉唑处理中更高。对研究绵羊静脉内给予泮托拉唑后,估计泮托拉唑的消除半衰期、分布容积和清除率分别为 3.29 小时、0.35 L/kg 和 65.26 mL/hr/kg。皮下给药后,最大浓度、达峰时间、消除半衰期和分布容积分别估计为 2604ng/mL、0.55 小时、2.48 小时和 0.37 L/kg。此外,生物利用度估计为 83.33%。静脉内或皮下给予泮托拉唑可能对成年绵羊的网胃溃疡的治疗或预防有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cec0/11168663/70ea57d30623/pone.0304533.g001.jpg

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