PDF(Pubmed)
Abstract：
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.
摘要：
腹部（胃）溃疡是绵羊的一种发病率，目前,据报道，该物种的胃保护剂药物的药代动力学和药效学数据很少。质子泵抑制剂埃索美拉唑已用于小动物和人类患者，通过增加胃pH来进行胃保护。本研究的目的是报道埃索美拉唑单次静脉给药后在绵羊体内的药代动力学参数和药效学效应。4只健康成年Southdown杂交母羊在以1.0mg/kg单次静脉注射埃索美拉唑后24小时内收集血液。在埃索美拉唑给药之前和之后24小时内采集鼻口液。分析血浆样本中埃索美拉唑和埃索美拉唑代谢物的浓度，埃索美拉唑砜高效液相色谱法。使用专用软件评估药代动力学和药效学数据。静脉给药后，埃索美拉唑迅速消除。消除半衰期，曲线下的面积,初始浓度（C0），间隙为0.2小时，1,197h*ng/mL，4,321ng/mL，和0.83毫升/小时/千克，分别。对于砜代谢物的消除半衰期，曲线下面积和最大浓度为0.16h，22.5h*ng/mL，和65.0ng/mL，分别。给药后1至6小时，口腔pH显着升高，并在给药后至少8小时保持在4.0以上。在这些绵羊中没有注意到不良反应。埃索美拉唑在绵羊体内迅速消除，类似于山羊。口腔pH值升高，但未来的研究需要制定埃索美拉唑在绵羊中使用的临床管理方法.
