Head and neck irradiation modulates pharmacokinetics of 5-fluorouracil and cisplatin

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• 作者：Chen-Hsi Hsieh (1) (2) (3)
  Mei-Ling Hou (2)
  Meng-Hsuan Chiang (2)
  Hung-Chi Tai (4)
  Hui-Ju Tien (1)
  Li-Ying Wang (7)
  Tung-Hu Tsai (2) (6)
  Yu-Jen Chen (2) (4) (5)
  
• 关键词：5 ; Fluorouracil (5 ; FU) ; Cisplatin (CDDP) ; Concurrent chemoradiation therapy (CCRT) ; Head and neck ; Pharmacokinetics ; Radiotherapy
• 刊名：Journal of Translational Medicine
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：11
• 期：1
• 全文大小：693 KB
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• 作者单位：Chen-Hsi Hsieh (1) (2) (3)
  Mei-Ling Hou (2)
  Meng-Hsuan Chiang (2)
  Hung-Chi Tai (4)
  Hui-Ju Tien (1)
  Li-Ying Wang (7)
  Tung-Hu Tsai (2) (6)
  Yu-Jen Chen (2) (4) (5)
  
  1. Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan
  2. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Li-Nong Street Section 2, Taipei, 112, Taiwan
  3. Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
  4. Department of Radiation Oncology, Mackay Memorial Hospital, 92, Chung-Shan North Road, Taipei, Taiwan
  7. School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan
  6. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
  5. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
  
• ISSN：1479-5876

文摘

Background 5-fluorouracil (5-FU) and cisplatin (CDDP) are used to enhance radiotherapy (RT) effect for head and neck (HN) cancers. However, the effect of local RT on systemic chemotherapeutics remains unclear. Here, we evaluated the influence of HN irradiation on the pharmacokinetics (PK) of 5-FU and CDDP in rats as experimental model. Methods The radiation dose distributions of HN cancer patients were determined for the low dose areas, which are generously deposited around the target volume. Two Gy and 0.5?Gy RT were selected. Single-fraction radiation was delivered to the HN of Sprague–Dawley rats. 5-FU at 100?mg/kg or CDDP at 5?mg/kg was intravenously infused 24?hours after radiation. Results Radiation at 2?Gy reduced the area under the plasma concentration vs. time curve (AUC) of 5-FU and CDDP by 16% and 29% compared to non-irradiated controls, respectively. This was accompanied by incremental total plasma clearance values. Intriguingly, low dose radiation at 0.5?Gy resulted in a similar pharmacokinetic profile, with a 17% and 33% reduction in the AUC of 5-FU and CDDP, respectively. The changes in AUC of bile, which increases with RT, were opposite to AUC of plasma for both drugs. Conclusions The local HN RT could modulate systemic PK of 5-FU and CDDP in rats. This unexpected RT-PK phenomena may provide a reference for adjustment of drug administration and is worthy of further investigation. Trial registration ClinicalTrials.gov ID NCT01755585 and NCT01609114