Fadel Charbel, Łebkowska-Wieruszewskac Beata, Serih Firas, Lisowski Andrew, Poapolathep Amnart, Giorgi Mario
Department of Veterinary Sciences, University of Pisa, Viale delle Piagge, 2, Pisa, PI 56124, Italy; Department of Veterinary Medicine, Lebanese University, Faculty of Agronomy Bldg., University Street, Dekwaneh, Beirut, Lebanon.
Department of Pharmacology, Toxicology and Environmental Protection, University of Life Sciences in Lublin, 13 Akademicka Street, Lublin 20-950, Poland.
Vet J. 2024 Jun;305:106138. doi: 10.1016/j.tvjl.2024.106138. Epub 2024 May 16.
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 V compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in C and T 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.
由于真胃溃疡对动物健康和生产力有影响,因此在集约化动物养殖中是一个重大问题。虽然泮托拉唑(PTZ)等质子泵抑制剂在治疗这些溃疡方面显示出前景,但关于PTZ在成年山羊和绵羊体内的药代动力学(PK)数据有限。本研究旨在通过调查和比较PTZ在这些物种单次静脉注射(IV)和皮下注射(SC)后的PK来填补这一空白。研究纳入了五只健康的雄性山羊和绵羊。使用经过验证的分析方法测定血浆样本中的PTZ浓度。进行了非房室分析,并对IV和SC给药之间以及不同物种之间进行了统计比较。无论给药途径如何,绵羊和山羊的全身暴露水平相似。然而,与山羊相比,绵羊由于V较高,t1/2较短。两种物种的Cl值相当,提取率值较低。两种物种在SC给药时的C和T没有显著差异,并且观察到完全生物利用度。两种物种的MAT均超过t1/2,表明存在潜在的反转现象。考虑到AUC作为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均无显著差异,可能无需在两种物种之间调整剂量。在实际应用中,SC给药更具实用性,与IV给药相比,不仅具有完全生物利用度,而且半衰期更长。有必要进一步研究探索PTZ在患有真胃溃疡的小型反刍动物中的PK/PD,以全面了解其在这种情况下的治疗效果。