Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics | Hsieh et al. Journal of Translational Medicine 2010 8 29 http content 8Z1 29 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics Chen-Hsi Hsiehf1 2 Yen-Ju HsieM 1 Chia-Yuan Liu1 4 Hung-ChiTai3 Yu-Chuen Huang7 8 Pei-Wei Shueng2 9 Le-Jung Wu2 Li-Ying Wang10 Tung-Hu Tsai 1 6 and Yu-Jen Chen 1 3 5 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 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 Gy representing a dose deposited in the generous off-target area in clinical practice resulted in a similar pharmacokinetic profile with a 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
