Biomedicine & Pharmacotherapy | |
Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats | |
Nobuyuki Sugioka1  Maiko Maekawa1  Saya Naito1  Azusa Futatsugi1  Keizo Fukushima1  Akira Okada2  | |
[1] Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan;Department of Regulatory Science, Faculty of Pharmacy, Musashino University, Tokyo, Japan; | |
关键词: Cisplatin; Split dose; Fractionated administration; Acute kidney injury; Chronic kidney disease; Hydration; | |
DOI : | |
来源: DOAJ |
【 摘 要 】
To prevent cisplatin (CDDP)-induced nephrotoxicity, co-treatment with massive hydration is essential for its clinical use. However, some patients are ineligible for this treatment. For such patients, a split dose of CDDP has been suggested as an alternative strategy. This study aimed to evaluate the nephrotoxicity of a split dose of CDDP by direct comparison with the conventional single dose of CDDP in rats. Rats were allocated to single- or split-dose groups. In the single-dose group, rats received the total dose of CDDP (from 0 to 7.5 mg/kg) with a single injection, whereas the same total dose of CDDP was split equally across five doses in the corresponding split-dose group. Blood samples were taken until day 21 after the first CDDP injection to monitor the plasma creatinine (Cr) concentration as an index of nephrotoxicity. CDDP-induced nephrotoxicities from day 1–10 and from day 15–21 were defined as acute kidney injury (AKI) and subchronic kidney injury (sCKI), respectively. The toxicity of CDDP-induced AKI in the split-dose group was found to be significantly lower than that in the single-dose group at any given total dose level. At a total dose of 7.5 mg/kg, a decrease of approximately 90% in AKI was found in the split-dose group, while the extent of attenuation of CDDP-induced sCKI in this group was approximately 30%. Our results provide evidence that a split-dose regimen could be an alternative strategy for CDDP-ineligible patients; however, the optimal regimen needs to be determined in future studies.
【 授权许可】
Unknown