Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats
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...
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Elsevier
2022-03-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222000075 |
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| author | Keizo Fukushima Azusa Futatsugi Maiko Maekawa Saya Naito Akira Okada Nobuyuki Sugioka |
| author_facet | Keizo Fukushima Azusa Futatsugi Maiko Maekawa Saya Naito Akira Okada Nobuyuki Sugioka |
| author_sort | Keizo Fukushima |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T21:01:19Z |
| format | Article |
| id | doaj.art-b127d850909a418e9853b797337223cc |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T21:01:19Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b127d850909a418e9853b797337223cc2022-12-22T04:03:30ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-03-01147112619Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to ratsKeizo Fukushima0Azusa Futatsugi1Maiko Maekawa2Saya Naito3Akira Okada4Nobuyuki Sugioka5Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, JapanDepartment of Regulatory Science, Faculty of Pharmacy, Musashino University, Tokyo, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan; Correspondence to: Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.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.http://www.sciencedirect.com/science/article/pii/S0753332222000075CisplatinSplit doseFractionated administrationAcute kidney injuryChronic kidney diseaseHydration |
| spellingShingle | Keizo Fukushima Azusa Futatsugi Maiko Maekawa Saya Naito Akira Okada Nobuyuki Sugioka Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats Biomedicine & Pharmacotherapy Cisplatin Split dose Fractionated administration Acute kidney injury Chronic kidney disease Hydration |
| title | Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats |
| title_full | Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats |
| title_fullStr | Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats |
| title_full_unstemmed | Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats |
| title_short | Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats |
| title_sort | comparison of cisplatin induced nephrotoxicity between single dose and split dose administration to rats |
| topic | Cisplatin Split dose Fractionated administration Acute kidney injury Chronic kidney disease Hydration |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222000075 |
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