Hsieh C.-H.Hsieh Y.-J.Liu C.-Y.Tai H.-C.Huang Y.-C.Shueng P.-W.Wu L.-J.LI-YING WANGTsai T.-H.Chen Y.-J.2020-06-292020-06-2920101479-5876https://www.scopus.com/inward/record.uri?eid=2-s2.0-77952302042&doi=10.1186%2f1479-5876-8-29&partnerID=40&md5=2205e104e626bed276744f20b515098ehttps://scholars.lib.ntu.edu.tw/handle/123456789/506318Background: 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.[SDGs]SDG3fluorouracil; 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-Dawleyjournal article10.1186/1479-5876-8-29203380602-s2.0-77952302042