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Type: Journal article
Title: Development of a rat model of oral small molecule receptor tyrosine kinase inhibitor-induced diarrhea
Author: Bowen, J.
Mayo, B.
Plews, E.
Bateman, E.
Stringer, A.
Boyle, F.
Finnie, J.
Keefe, D.
Citation: Cancer Biology & Therapy, 2012; 13(13):1269-1275
Publisher: Landes Bioscience
Issue Date: 2012
ISSN: 1538-4047
Statement of
Joanne M. Bowen, Bronwen J. Mayo, Erin Plews, Emma Bateman, Andrea M. Stringer, Frances M. Boyle, John W. Finnie and Dorothy M.K. Keefe
Abstract: Orally administered small molecule receptor tyrosine kinase inhibitors (RTKIs) are increasingly common treatments for cancer, both alone and in combination with chemotherapy. However, their side effect profiles and the underlying mechanisms of such are not yet fully elucidated. Management of their most common dose limiting side effect, diarrhea, has been hampered by a lack of suitable animal models. We aimed to develop a clinically relevant rat model of RTKI-induced diarrhea that could be utilized for investigating supportive care interventions and pharmacokinetics. Albino Wistar rats were treated daily for 4 weeks with various concentrations of lapatinib to determine the optimal dose for development of diarrhea. This was then followed by an experiment with addition of paclitaxel once weekly for 4 weeks to observe effects of combination drug treatment on diarrhea. Data regarding animal tolerance to the treatment, organ weights, circulating lapatinib concentration and histopathology were collected weekly. Lapatinib caused diarrhea in rats that was dose-dependent. Diarrhea occurred without causing significant intestinal histopathology. Follow up experiments are currently underway to determine the exact pathogenesis and mechanisms of lapatinib-induced diarrhea and potential protective strategies.
Keywords: diarrhea; intestine; lapatinib; rat model
Rights: ©2012 Laudes Bioscience
RMID: 0020122832
DOI: 10.4161/cbt.21783
Appears in Collections:Medical Sciences publications

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