Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
J Transl Med. 2010 Mar 25;8:29. doi: 10.1186/1479-5876-8-29.
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.
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.
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.
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.
含氟尿嘧啶（5-FU）的同期放化疗广泛用于治疗腹部恶性肿瘤。然而，辐射与 5-FU 之间的相互作用仍不清楚。我们评估了腹部照射对大鼠 5-FU 药代动力学的影响。
根据低剂量区域（大量分布在肝内靶区周围）确定胆管癌患者的放射剂量分布，然后使用基于计算机断层扫描的计划从直线加速器对整个腹部给予相应的单次放射剂量。在放射后 24 小时，经静脉注射 5-FU 100mg/kg。使用配备紫外检测器的高效液相色谱系统测量血液中的 5-FU。采用超滤法测量蛋白结合的 5-FU。
2Gy 的照射（模拟每日人体治疗剂量）使 5-FU 的血浆浓度-时间曲线下面积（AUC）与未照射对照相比减少了 31.7%。这伴随着平均驻留时间和增量总血浆清除率值以及稳态分布容积的减少。有趣的是，0.5Gy 的低剂量照射（代表在临床实践中大量分布的靶外区域的剂量）导致了相似的药代动力学特征，AUC 减少了 21.4%。这种效应与蛋白结合能力无关。
腹部照射似乎显著调节 5-FU 的全身药代动力学，既针对靶区治疗剂量，也针对靶外区域。这种意外和不需要的影响值得进一步研究，在临床实践中可能需要考虑。
