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Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
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- Keisuke Mine
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Takehiro Kawashiri
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Mizuki Inoue
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Daisuke Kobayashi
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Kohei Mori
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Shiori Hiromoto
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Hibiki Kudamatsu
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Mayako Uchida
- Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe 610-0395, Japan
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- Nobuaki Egashira
- Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan
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- Satoru Koyanagi
- Department of Local Healthcare Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Shigehiro Ohdo
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Takao Shimazoe
- Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Description
<jats:p>(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5–20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32–0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.</jats:p>
Journal
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 23 (16), 8859-, 2022-08-09
MDPI AG