Cisplatin (CDDP) is a typical drug that causes drug-induced hearing loss. CDDP is taken up into the inner ear cells via the organic cation transporter (OCT)2 and is thought to be cytotoxic, but the details are unknown. In this study, we searched for preventive drugs against CDDP-induced hearing loss using medical data and evaluated the efficacy of the preventive drugs found. Imbalance analysis was performed using data from FAERS, the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System, and VigiBase, the World Health Organization (WHO) adverse event reporting database, to identify candidate preventive drugs based on the reported odds ratio (ROR) and 95% confidence interval (CI) of “hearing impairment” with CDDP use. Based on the analysis of both databases, the 5-HT3 receptor antagonist palonosetron was selected as a candidate for preventive drugs for CDDP-induced hearing loss. CDDP (15 mg/kg) was administered intraperitoneally twice to mice and the auditory brainstem response (ABR) was measured 3 days after the last dose. Palonosetron (15 mg/kg) was administered intraperitoneally 30 minutes before each dose of CDDP. CDDP administration to mice caused significant hearing loss at 8, 16, and 32 kHz frequencies. In contrast, palonosetron significantly suppressed hearing impairment at all frequencies. These results suggest that palonosetron may be a useful preventive drug against CDDP-induced hearing loss.
