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Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics

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: Th...

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Autores principales: Hsieh, Chen-Hsi, Hsieh, Yen-Ju, Liu, Chia-Yuan, Tai, Hung-Chi, Huang, Yu-Chuen, Shueng, Pei-Wei, Wu, Le-Jung, Wang, Li-Ying, Tsai, Tung-Hu, Chen, Yu-Jen
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861020/
https://www.ncbi.nlm.nih.gov/pubmed/20338060
http://dx.doi.org/10.1186/1479-5876-8-29
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author Hsieh, Chen-Hsi
Hsieh, Yen-Ju
Liu, Chia-Yuan
Tai, Hung-Chi
Huang, Yu-Chuen
Shueng, Pei-Wei
Wu, Le-Jung
Wang, Li-Ying
Tsai, Tung-Hu
Chen, Yu-Jen
author_facet Hsieh, Chen-Hsi
Hsieh, Yen-Ju
Liu, Chia-Yuan
Tai, Hung-Chi
Huang, Yu-Chuen
Shueng, Pei-Wei
Wu, Le-Jung
Wang, Li-Ying
Tsai, Tung-Hu
Chen, Yu-Jen
author_sort Hsieh, Chen-Hsi
collection PubMed
description 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.
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spelling pubmed-28610202010-04-29 Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics Hsieh, Chen-Hsi Hsieh, Yen-Ju Liu, Chia-Yuan Tai, Hung-Chi Huang, Yu-Chuen Shueng, Pei-Wei Wu, Le-Jung Wang, Li-Ying Tsai, Tung-Hu Chen, Yu-Jen J Transl Med Research 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. BioMed Central 2010-03-25 /pmc/articles/PMC2861020/ /pubmed/20338060 http://dx.doi.org/10.1186/1479-5876-8-29 Text en Copyright ©2010 Hsieh et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Hsieh, Chen-Hsi
Hsieh, Yen-Ju
Liu, Chia-Yuan
Tai, Hung-Chi
Huang, Yu-Chuen
Shueng, Pei-Wei
Wu, Le-Jung
Wang, Li-Ying
Tsai, Tung-Hu
Chen, Yu-Jen
Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title_full Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title_fullStr Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title_full_unstemmed Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title_short Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics
title_sort abdominal irradiation modulates 5-fluorouracil pharmacokinetics
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861020/
https://www.ncbi.nlm.nih.gov/pubmed/20338060
http://dx.doi.org/10.1186/1479-5876-8-29
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