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目的:二氢嘧啶脱氢酶(DPD)缺乏是导致5-FU毒性的主要原因。我们根据病人DPD状态调节5-FU的使用剂量,减少了毒副作用而没有影响疗效。当前的工作目标是确定5-FU药动学的合变量并为它建立一个新的模型。方法:本研究纳入22个头颈部肿瘤患者,根据DPD状态调节5-FU的剂量,利用NONMEM V5计算群体和个体的药动学参数。结果:在本组病人中,5-FU的药动学被描述为线性的、利用一级条件评估法和混合误差模型构成的一室模型。影响5-FU清除的主要合变量首先是体表面积。DPD状态对5-FU清除的影响出现在64%的病人中。DPD状态比年龄、性别等经常与5-FU毒性相关的合变量更能影响5-FU的清除。结论:在基于DPD的5-FU剂量调整战略的病人中,预先确定DPD不足的病人已被初筛并调整剂量,从而影响了5-FU的药动学。当DPD的问题被预先处理后,体表面积成为调节5-FU剂量的相关合变量。
Aim: Dihydropyrimidine dehydrogenase (DPD) deficiency is the leading cause of 5-FU toxicity. We adjust the dose of 5-FU according to the patient’s DPD status, reducing the toxic and side effects without affecting the curative effect. The current goal is to determine the combined variables of 5-FU pharmacokinetics and establish a new model for it. METHODS: Twenty-two patients with head and neck cancer were enrolled in this study. The dose of 5-FU was adjusted according to the state of DPD and the pharmacokinetic parameters of both groups and individuals were calculated using NONMEM V5. RESULTS: Pharmacokinetics of 5-FU in this group of patients was described as a linear one-compartment model using a first-order conditional assessment and a mixed-error model. The main covariates influencing 5-FU clearance are primarily body surface area. The effect of DPD status on 5-FU clearance appears in 64% of patients. The covariates associated with 5-FU toxicity, such as age, gender, and DPD status are more likely to influence 5-FU clearance. CONCLUSIONS: Among DPD-based 5-FU dose-adjusting strategies, pre-determined DPD-deficient patients have been screened and dose adjusted, affecting 5-FU pharmacokinetics. When the problem of DPD is pre-treated, the body surface area becomes the relevant covariate that regulates the 5-FU dose.