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Dosing Time-Dependent Effects of Paclitaxel on Peripheral Neuropathy in Mice
Yoshihiro Seto1, Koichi Miyamoto2, Daisuke Inoue2
1Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan; yoshseto@pha.u-toyama.ac.jp.
Anticancer Research
|August 1, 2025
Summary
Timing paclitaxel (PTX) administration can reduce chemotherapy-induced nerve pain. Giving PTX at 9:00 caused more pain, while 21:00 dosing led to quicker recovery from mechanical allodynia in mice.
Area of Science:
- Pharmacology
- Neuroscience
- Chronobiology
Background:
- Paclitaxel (PTX) is a vital chemotherapy agent.
- Peripheral neuropathy, specifically mechanical allodynia, is a common PTX side effect.
- Understanding PTX's side effects is crucial for optimizing cancer therapy.
Purpose of the Study:
- To investigate the efficacy of chronotherapy in mitigating PTX-induced mechanical allodynia.
- To explore the impact of drug administration timing on PTX neurotoxicity.
Main Methods:
- Male C57BL/6J mice received intravenous PTX at various times (1:00, 5:00, 9:00, 13:00, 17:00, 21:00).
- Mechanical allodynia was quantified using the Von Frey test.
- Plasma PTX concentrations were measured 12 hours post-administration.
Main Results:
- Circadian variations in mechanical allodynia were significant, with the 9:00 PTX group exhibiting the lowest withdrawal threshold.
- The 21:00 PTX group showed earlier recovery from mechanical allodynia compared to the 9:00 group.
- Higher plasma PTX levels at 12 hours were observed in the 9:00 group, indicating circadian influence on drug metabolism.
Conclusions:
- Chronotherapy, specifically timing PTX administration, can effectively ameliorate mechanical allodynia in mice.
- Optimizing PTX administration schedules may improve patient outcomes by reducing neurotoxicity.
- Further research into PTX pharmacokinetics and antitumor effects under chronotherapy is warranted.
