Dacomitinib, a second-generation tyrosine kinase inhibitor, was irreversible inhibitor forming covalent bonds with the kinase domains of EGFR and other ErbB family receptors. Dacomitinib has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer. In this study, we aimed to develop an immunohistochemistry to detect dacomitinib-ErbB family receptor conjugates. Immunostaining was performed in rat intestine and skin tissues after oral administration of dacomitinib. Following a single oral dose of dacomitinib, strong staining was observed after 24 hr in the ileum and colon, with only slight staining in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, hair follicles, and sebaceous glands. Moreover, significant amounts of dacomitinib remained for up to 72 hr post-administration in the ileum, colon, and skin. This report is the first to elucidate the localization and accumulation of dacomitinib in the rat intestine and skin and should be valuable during efforts to clarify the mechanism dacomitinib-induced diarrhea or skin toxicities.

中文翻译：

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达可替尼在大鼠肠和皮肤中的免疫组织化学定位和蓄积研究。

第二代酪氨酸激酶抑制剂Dacomitinib是不可逆的抑制剂，与EGFR和其他ErbB家族受体的激酶结构域形成共价键。达可替尼已被批准用于治疗局部晚期或转移性非小细胞肺癌。在这项研究中，我们旨在开发一种免疫组织化学方法来检测达可替尼-ErbB家族受体结合物。口服达科替尼后在大鼠肠和皮肤组织中进行免疫染色。单次口服达科替尼的剂量后，在回肠和结肠中24小时后观察到强烈的染色，而在十二指肠和空肠中只有轻微的染色。在皮肤中，在表皮，毛囊和皮脂腺中观察到强烈的染色。此外，回肠，结肠和皮肤给药后最多72小时仍保留大量达科替尼。该报告是第一个阐明达科替尼在大鼠肠道和皮肤中的定位和积累的报告，在阐明达科替尼引起的腹泻或皮肤毒性的机理研究中应该是有价值的。