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静脉注射后山羊体内泮托拉唑和泮托拉唑砜的药代动力学:初步报告

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report.

作者信息

Smith Joe S, Mochel Jonathan P, Soto-Gonzalez Windy M, Rahn Rebecca R, Fayne Bryanna N, Escher Olivia G, Geletka Anastasia M, Harvill Lainey E, Bergman Joan B, Cox Sherry

机构信息

Systems Modeling and Reverse Translational Pharmacology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

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

出版信息

Front Vet Sci. 2021 Sep 22;8:744813. doi: 10.3389/fvets.2021.744813. eCollection 2021.

Abstract

Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hrμg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

摘要

反刍动物有发生皱胃溃疡的风险,但对于山羊等抗溃疡疗法(如质子泵抑制剂泮托拉唑),缺乏药代动力学数据。主要研究目的是估计成年山羊静脉注射泮托拉唑后的血浆药代动力学参数。次要目的是描述山羊体内代谢产物泮托拉唑砜的药代动力学参数。以1mg/kg的剂量对6只成年山羊静脉注射泮托拉唑。在36小时内采集血浆样本,并通过反相高效液相色谱法分析,以测定泮托拉唑和泮托拉唑砜的浓度。通过非房室分析确定药代动力学参数。静脉注射后,泮托拉唑的血浆清除率、消除半衰期和分布容积分别估计为0.345mL/kg/min、0.7小时和0.9L/kg。泮托拉唑砜的最大浓度、消除半衰期和曲线下面积分别估计为0.1μg/mL、0.8小时和0.2hrμg/mL。总体提取率估计为0.00795±0.00138。研究结束后,所有动物的体格检查均正常。报道的泮托拉唑血浆清除率低于驹、犊牛和羊驼的报道值。消除半衰期似乎比驹和犊牛的报道值短。未来需要进行药效学研究,以确定泮托拉唑对山羊胃酸抑制的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b15/8492921/1b12d81a5dc3/fvets-08-744813-g0001.jpg

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