Abstract
Background/Aim: Oxaliplatin-induced chronic neuropathy is a prominent factor for dose reduction and not completing all cycles of chemotherapy for patients with colorectal cancer (CRC). The aim of the study was to investigate the pharmacokinetics and toxicodynamics of oxaliplatin-induced chronic neuropathy in CRC rats to ensure effective management. Materials and Methods: A rat model of CRC was developed using 1,2-Dimethylhydrazine and dextran sulfate. Oxaliplatin (L-OHP) was administered intravenously to CRC rats every week. The pharmacokinetic profiles and tumor distribution of L-OHP and chronic neuropathies were investigated for over four weeks. Results: The mean values of the area under the concentration-time curve for L-OHP showed a dose-dependent increase. Chronic neuropathy occurred from Day 14 in the 8 mg/kg group and Day 19 in the 3 and 5 mg/kg groups. Conclusion: These results provide preliminary information for the development of a pharmacokinetic and toxicodynamic model of L-OHP for CRC therapy cycles.
- Oxaliplatin (L-OHP)
- chronic neuropathy
- tumor shrinkage
- pharmacokinetic
- toxicodynamic
- colorectal cancer rat model
Footnotes
Authors' Contributions
Yukako Ito: Conception and design of this study, drafting of the article and critical revision of the article for important intellectual content; Shinji Kobuchi: Analysis and interpretation of data; Waki Takesada: Collection and assembly of data of mechanical allodynia; Chiharu Takahashi: Collection and assembly of data of pharmacokinetic and tumor tissue samples.
Conflicts of Interest
Y. Ito, S. Kobuchi, W. Takesada, and C. Takahashi declare that they have no conflicts of interest.
Funding
This study was supported by a Grant-in-Aid for Scientific Research (C) from JSPS KAKENHI, Grant Number 15K08085.
- Received April 26, 2019.
- Revision received June 21, 2019.
- Accepted June 24, 2019.
- Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved