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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Time-dependent pharmacokinetics of 5-fluorouracil and association with treatment tolerability in the adjuvant setting of colorectal cancer.
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Time-dependent pharmacokinetics of 5-fluorouracil and association with treatment tolerability in the adjuvant setting of colorectal cancer.

机译：5-氟尿嘧啶的时间依赖性药代动力学及其在结直肠癌辅助治疗中的治疗耐受性。

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摘要

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.
机译：作者评估了5-氟尿嘧啶（5-FU）对81例接受5-FU静脉内加亚叶酸辅助治疗的大肠癌患者的耐受性的影响，共6个周期。在第一个化疗周期的第1天和第5天，推注后5分钟和45分钟测量了5-FU及其非活性代谢物5-氟-5,6-二氢尿嘧啶（5-FDHU）的药代动力学。第5天的5-FU清除率（62.64±20.16 L / h / m（2））明显低于第1天（74.83±31.61 L / h / m（2））。较低的5-FU清除值也预示了整个化疗过程中的副作用。特别是，第1天清除率值较低的患者在第5天该参数进一步降低，并伴有严重毒性。总之，5-FU会改变其清除率，这可能部分是由于5-FDHU生物转化的减少。这些发现对不良代谢者具有安全意义，这些不良代谢者在重复治疗周期中药物清除率可能低于阈值。

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