Localization and Accumulation Studies of Dacomitinib in Rat Intestines and Skin by Immunohistochemistry

2019 The Japan Society of Histochemistry and Cytochemistry..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:52

Enthalten in:

Acta histochemica et cytochemica - 52(2019), 6 vom: 27. Dez., Seite 101-106

Sprache:

Englisch

Beteiligte Personen:

Yamamoto, Yutaro [VerfasserIn]
Saita, Tetsuya [VerfasserIn]
Oka, Asuki [VerfasserIn]
Kataoka, Hiroto [VerfasserIn]
Shin, Masashi [VerfasserIn]

Links:

Volltext

Themen:

Dacomitinib
Immunohistochemistry
Intestine
Journal Article
Localization
Skin

Anmerkungen:

Date Revised 28.09.2020

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1267/ahc.19031

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM305977008