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Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
Chen-Hsi Hsieh1, Yen-Ju Hsieh, Chia-Yuan Liu
1Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Journal of Translational Medicine
|March 27, 2010
Summary
Abdominal irradiation significantly alters the pharmacokinetics of 5-fluorouracil (5-FU) in rats. Both therapeutic and off-target radiation doses reduced 5-FU levels, suggesting potential clinical implications.
Area of Science:
- Pharmacology
- Radiation Oncology
- Cancer Treatment
Background:
- Concurrent chemoradiation with 5-fluorouracil (5-FU) is a standard treatment for abdominal malignancies.
- The precise interactions between radiation and 5-FU pharmacokinetics are not fully understood.
- This study investigates the impact of abdominal irradiation on 5-FU pharmacokinetics.
Purpose of the Study:
- To evaluate how abdominal irradiation affects the systemic pharmacokinetics of 5-fluorouracil (5-FU).
- To determine if radiation doses used in clinical settings influence 5-FU drug levels.
- To explore the relationship between radiation exposure and 5-FU metabolism.
Main Methods:
- Whole-body abdominal irradiation was administered to Sprague-Dawley rats using a linear accelerator.
- 5-fluorouracil (5-FU) was intravenously infused 24 hours post-irradiation.
- High-performance liquid chromatography (HPLC) and ultrafiltration were used to measure 5-FU plasma concentrations and protein binding.
Main Results:
- A 2 Gy radiation dose, simulating clinical treatment, reduced the 5-FU area under the curve (AUC) by 31.7%.
- Lower doses (0.5 Gy) of radiation, representing off-target exposure, also decreased 5-FU AUC by 21.4%.
- These pharmacokinetic changes were observed independently of protein binding.
Conclusions:
- Abdominal irradiation significantly alters 5-FU pharmacokinetics at both therapeutic and off-target radiation levels.
- The observed modulation of 5-FU levels by radiation is unexpected and warrants further investigation.
- These findings may necessitate adjustments in clinical practice for concurrent chemoradiation involving 5-FU.
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