Polpharma Biologics SA, 80-172 Gdańsk, Poland.
Sub-Department of Pharmacology, Toxicology and Environmental Protection, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland.
J Vet Sci. 2021 Sep;22(5):e47. doi: 10.4142/jvs.2021.22.e47. Epub 2021 May 27.
Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs.
This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1.
The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold.
The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different ( > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold.
Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.
由于人类和猪皮在结构和生理学上有许多相似之处，因此猪模型对于皮下给药后生物药物的生物测试非常有用。对皮下注射部位差异的了解可能会对生物药物的吸收阶段和药代动力学特征产生重大影响。
本研究旨在分析单次皮下给予乌司奴单抗后，给药部位对猪药代动力学和选定生化及血液学参数的影响。通过酶联免疫吸附试验分析血浆中的药物浓度。基于原始数据，使用 Phoenix WinNonlin 8.1 软件和 ThothPro v 4.1 进行药代动力学分析。
该研究纳入了 12 头健康、雌性大白猪。每组猪均接受单次 1 mg/kg 乌司奴单抗皮下注射，注射部位分别为腹股沟内褶的内部或外部。
腹股沟内褶内部和外部的吸收速率差异不显著。然而，两组之间达峰时间、清除率、从 0 到平均驻留时间的曲线下面积和平均驻留时间差异显著（>0.05）。与腹股沟内褶内部给药相比，乌司奴单抗外部给药的相对生物利用度降低了 40.36%。
健康繁殖猪是研究皮下给予乌司奴单抗药代动力学特征的相关模型。
