Osteoncology Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
J Clin Pharmacol. 2012 Mar;52(3):361-9. doi: 10.1177/0091270010396710. Epub 2011 Mar 7.
The authors evaluated the influence of 5-fluorouracil (5-FU) on treatment tolerability in 81 colorectal cancer patients given adjuvant 5-FU intravenously plus folinic acid for 6 cycles. The pharmacokinetics of 5-FU and its inactive metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) were measured on days 1 and 5 of the first chemotherapy cycle, 5 and 45 minutes after bolus administration. 5-FU clearance was significantly lower on day 5 (62.64 ± 20.16 L/h/m(2)) than on day 1 (74.83 ± 31.61 L/h/m(2)). The lower 5-FU clearance values also predicted the side effects during the entire course of chemotherapy. In particular, patients with low clearance values on day 1 had a further reduction in this parameter on day 5, associated with severe toxicities. In conclusion, 5-FU alters its clearance, which could be partly due to a reduction in 5-FDHU biotransformation. These findings have safety implications for poor metabolizers whose drug clearance may fall below the threshold during repeated treatment cycles.
作者评估了 5-氟尿嘧啶（5-FU）对 81 例接受辅助静脉注射 5-FU 和叶酸治疗 6 个周期的结直肠癌患者治疗耐受性的影响。在第 1 个化疗周期的第 1 天和第 5 天，在推注后 5 分钟和 45 分钟测量了 5-FU 和其无活性代谢物 5-氟-5,6-二氢尿嘧啶（5-FDHU）的药代动力学。第 5 天（62.64 ± 20.16 L/h/m2）的 5-FU 清除率明显低于第 1 天（74.83 ± 31.61 L/h/m2）。较低的 5-FU 清除率值也预测了整个化疗过程中的副作用。特别是在第 1 天清除率值较低的患者，第 5 天该参数进一步降低，与严重毒性相关。总之，5-FU 改变了其清除率，这可能部分归因于 5-FDHU 生物转化的减少。这些发现对药物清除率可能在重复治疗周期中低于阈值的代谢不良者具有安全性意义。
