Comparative pharmacokinetics of intravenous and subcutaneous pantoprazole in sheep and goats

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES
Charbel Fadel , Beata Łebkowska-Wieruszewskac , Firas Serih , Andrew Lisowski , Amnart Poapolathep , Mario Giorgi
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Abstract

Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher Vd compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in Cmax and Tmax between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.

绵羊和山羊静脉注射和皮下注射泮托拉唑的药代动力学比较
由于腹腔溃疡会影响动物健康和生产率,因此是集约化畜牧业的一个重大问题。虽然泮托拉唑(PTZ)等质子泵抑制剂(PPI)有望治疗这些溃疡,但有关 PTZ 在成年山羊和绵羊体内药代动力学(PK)的数据却很有限。本研究旨在通过调查和比较 PTZ 在这些物种体内单次静脉注射(IV)和皮下注射(SC)后的 PK 值来填补这一空白。研究对象包括五只健康的雄性山羊和绵羊。血浆样本中的 PTZ 浓度是通过有效的分析方法测定的。研究人员进行了非室分析,并对静脉注射和皮下注射以及不同物种之间进行了统计比较。无论采用哪种给药途径,绵羊和山羊的全身暴露水平相似。不过,与山羊相比,绵羊的 Vd 较高,因此 t1/2 较短。两种动物的 Cl 值相当,萃取比值较低。绵羊和山羊的给药 Cmax 和 Tmax 没有明显差异,生物利用度完全一致。两种药物的 MAT 均超过了 t1/2,表明可能存在翻转现象。考虑到 AUC 是药物疗效的预测指标,并且观察到绵羊和山羊在任何给药途径下的全身暴露量都没有显著差异,因此可能没有必要对这两种动物进行剂量调整。在野外环境中,静脉注射证明更为实用,不仅生物利用度高,而且半衰期也比静脉注射长。有必要进一步研究 PTZ 在患有腹腔溃疡的小型反刍动物中的 PK/PD,以充分了解其在此类情况下的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Veterinary journal
Veterinary journal 农林科学-兽医学
CiteScore
4.10
自引率
4.50%
发文量
79
审稿时长
40 days
期刊介绍: The Veterinary Journal (established 1875) publishes worldwide contributions on all aspects of veterinary science and its related subjects. It provides regular book reviews and a short communications section. The journal regularly commissions topical reviews and commentaries on features of major importance. Research areas include infectious diseases, applied biochemistry, parasitology, endocrinology, microbiology, immunology, pathology, pharmacology, physiology, molecular biology, immunogenetics, surgery, ophthalmology, dermatology and oncology.
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