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ID 116008
Title Alternative
EFFECTS OF 5-HT₃ RAS ON CDDP-INDUCED AKI
Author
Kanda, Masaya Tokushima University
Yoshioka, Toshihiko Tokushima University
Yoshida, Ami Tokushima University
Murai, Yoichi Tokushima University
Niimura, Takahiro Tokushima University
Chuma, Masayuki Asahikawa Medical University
Content Type
Journal Article
Description
Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.
Journal Title
Clinical and Translational Science
ISSN
17528062
NCID
AA12625737
Publisher
Wiley|American Society for Clinical Pharmacology and Therapeutics
Published Date
2021-05-13
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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DOI (Published Version)
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FullText File
cts.pdf 599 KB
language
eng
TextVersion
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departments
University Hospital
Medical Sciences
Pharmaceutical Sciences