Department of Internal Medicine, Gastroenterology Division, IBD Unit, Catholic University of the Sacred Heart, Rome, Italy.
Dig Liver Dis. 2013 Dec;45(12):1017-21. doi: 10.1016/j.dld.2013.06.007. Epub 2013 Aug 2.
Infliximab is effective in human and murine IBD, but its pharmacodynamic is still poorly known. The aim of this study was to assess the affinity of infliximab to murine TNF-α, its role in murine colitis when administered intra-rectally and its levels in the blood, gut mucosa and stool of healthy and sick mice.
An ELISA kit was built in order to assess the affinity of infliximab to human or murine-TNF-α. Human IgG were used as controls. DSS model of colitis on C57BL/6 mice was used to assess clinical efficacy of infliximab administered intravenously or by enema. Stool, serum and colon samples were collected to assess infliximab levels and histology for Rachmilewitz score.
Infliximab showed a good affinity both for human-TNF-α and murine-TNF-α. In DSS colitic mice infliximab ameliorated the severity of colitis, regardless of the administration route. In comparison with colitic mice, healthy mice displayed higher serum and mucosal infliximab levels, while detectable levels of infliximab were found in faeces, particularly in colitic mice.
Our data support murine models to study infliximab pharmacokinetics and dynamics. Measurable levels of infliximab can be found at different concentrations in blood, intestinal mucosa and stool from healthy and sick mice, thus infliximab pharmacokinetics could have a major impact in human IBD.
英夫利昔单抗在人类和鼠类的 IBD 中均有效，但它的药效动力学仍知之甚少。本研究的目的是评估英夫利昔单抗与鼠 TNF-α 的亲和力，评估其在直肠内给药时对鼠结肠炎的作用，以及评估其在健康和患病小鼠的血液、肠道黏膜和粪便中的水平。
构建了 ELISA 试剂盒以评估英夫利昔单抗与人或鼠 TNF-α 的亲和力。用人 IgG 作为对照。采用 DSS 结肠炎模型研究静脉内或直肠内给予英夫利昔单抗的临床疗效。收集粪便、血清和结肠样本，以评估英夫利昔单抗的水平和 Rachmilewitz 评分的组织学。
英夫利昔单抗与人 TNF-α 和鼠 TNF-α 均具有良好的亲和力。在 DSS 结肠炎小鼠中，英夫利昔单抗无论给药途径如何，均能改善结肠炎的严重程度。与结肠炎小鼠相比，健康小鼠的血清和黏膜英夫利昔单抗水平更高，而在粪便中可检测到英夫利昔单抗，尤其是在结肠炎小鼠中。
我们的数据支持使用鼠模型来研究英夫利昔单抗的药代动力学和药效动力学。可在来自健康和患病小鼠的血液、肠道黏膜和粪便中以不同浓度检测到英夫利昔单抗，因此英夫利昔单抗的药代动力学可能对人类 IBD 产生重大影响。
