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  1. NTU Scholars
  2. 醫學院
  3. 物理治療學系所
Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/506318
Title: Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
Authors: Hsieh C.-H.
Hsieh Y.-J.
Liu C.-Y.
Tai H.-C.
Huang Y.-C.
Shueng P.-W.
Wu L.-J.
LI-YING WANG 
Tsai T.-H.
Chen Y.-J.
Issue Date: 2010
Journal Volume: 8
Start page/Pages: 29
Source: Journal of Translational Medicine
Abstract: 
Background: Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for treatment of abdominal malignancy. Nonetheless, the interactions between radiation and 5-FU remain unclear. We evaluated the influence of abdominal irradiation on the pharmacokinetics of 5-FU in rats.Methods: The radiation dose distributions of cholangiocarcinoma patients were determined for the low dose areas, which are generously deposited around the intrahepatic target volume. Then, corresponding single-fraction radiation was delivered to the whole abdomen of Sprague-Dawley rats from a linear accelerator after computerized tomography-based planning. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. A high-performance liquid chromatography system equipped with a UV detector was used to measure 5-FU in the blood. Ultrafiltration was used to measure protein-unbound 5-FU.Results: Radiation at 2 Gy, simulating the daily human treatment dose, reduced the area under the plasma concentration vs. time curve (AUC) of 5-FU by 31.7% compared to non-irradiated controls. This was accompanied by a reduction in mean residence time and incremental total plasma clearance values, and volume of distribution at steady state. Intriguingly, low dose radiation at 0.5 Gy, representing a dose deposited in the generous, off-target area in clinical practice, resulted in a similar pharmacokinetic profile, with a 21.4% reduction in the AUC. This effect was independent of protein binding capacity.Conclusions: Abdominal irradiation appears to significantly modulate the systemic pharmacokinetics of 5-FU at both the dose level for target treatment and off-target areas. This unexpected and unwanted influence is worthy of further investigation and might need to be considered in clinical practice. ? 2010 Hsieh et al; licensee BioMed Central Ltd.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-77952302042&doi=10.1186%2f1479-5876-8-29&partnerID=40&md5=2205e104e626bed276744f20b515098e
https://scholars.lib.ntu.edu.tw/handle/123456789/506318
ISSN: 1479-5876
DOI: 10.1186/1479-5876-8-29
SDG/Keyword: fluorouracil; antineoplastic antimetabolite; abdominal radiotherapy; animal experiment; area under the curve; article; controlled study; drug blood level; drug clearance; drug distribution; drug elimination; drug half life; drug protein binding; human; nonhuman; radiation dose; radiation dose distribution; rat; tomotherapy; abdominal tumor; animal; bile duct carcinoma; dose response; drug effect; liver; male; metabolism; multimodality cancer therapy; radiation exposure; radiation response; Sprague Dawley rat; Abdominal Neoplasms; Animals; Antimetabolites, Antineoplastic; Area Under Curve; Cholangiocarcinoma; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Fluorouracil; Humans; Liver; Male; Rats; Rats, Sprague-Dawley
[SDGs]SDG3
Appears in Collections:物理治療學系所

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臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

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