| 5-氟尿嘧啶在头颈部肿瘤病人体内的群体药动学研究 |
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| 引用本文： | 杨晨光1,Ciccolini Josephe2,许 鹏1,鱼麦侠1,谢燕华1,孙 婧1,Mercier Cedric3,陈 捷1. 5-氟尿嘧啶在头颈部肿瘤病人体内的群体药动学研究[J]. 现代肿瘤医学, 2013, 0(12): 2661-2666. DOI: 10.3969/j.issn.1672-4992.2013.12.06 |
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| 作者姓名： | 杨晨光1 Ciccolini Josephe2 许 鹏1 鱼麦侠1 谢燕华1 孙 婧1 Mercier Cedric3 陈 捷1 |
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| 作者单位： | 1.陕西省中医医院肿瘤科，陕西 西安 710002;2.La Timone大学医院临床和药理学联盟，法国 Marseille 13385;3.La Timone大学医院肿瘤内科，法国 Marseille 13385 |
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| 基金项目： | 陕西省科学研究发展计划支持项目（编号:2011k13-01-06） |
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| 摘 要： | 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。
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| 关 键 词： | 群体药物动力学 二氢嘧啶脱氢酶（DPD） 头颈部肿瘤 NONMEM分析 |
5-Fluorourouracil in head and neck cancer:a popupation pharmacokinetics study |
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| Yang Chenguang1,Ciccolini Josephe2,Xu Peng1,Yu Maixia1,Xie Yanhua1,Sun Jing1,Mercier Cedric3,Chen Jie1. 5-Fluorourouracil in head and neck cancer:a popupation pharmacokinetics study[J]. Journal of Modern Oncology, 2013, 0(12): 2661-2666. DOI: 10.3969/j.issn.1672-4992.2013.12.06 |
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| Authors: | Yang Chenguang1 Ciccolini Josephe2 Xu Peng1 Yu Maixia1 Xie Yanhua1 Sun Jing1 Mercier Cedric3 Chen Jie1 |
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| Affiliation: | 1.Department of Oncology，Shaanxi Province Chinese Traditionnal Medecine Hospital，Shaanxi Xi'an 710002，China；2.Federation de Pharmacologie Medicale et Clinique，La Timone University Hospital，Marseille 13385，France；3Medical Oncology Unit，La Timone University Hospital，Marseille 13385，France. |
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| Abstract: | Objective:A major cause for 5-FU severe toxicities is a pharmacogenetic syndrome known as dihydropyrimidine dehydrogenase（DPD）deficiency，affecting the ability of patients to detoxify standard dosages.5-FU dosage was adjusted in patients in accordance with their DPD status，thus reducing toxicity without affecting treatment efficacy.The present work aims at identifying the effect of covariates on 5-FU pharmacokinetics（PK）and developing a new model for it.Methods:This retrospective study was carried out on 22 patients treated for head and neck cancer with adjusting dosage of 5-FU.Population and individual pharmacokinetics parameters were computed using a NONMEM V5 program.Result:In all patients，pharmacokinetics of 5-FU was best described by a linear，one compartment model using first order conditional estimation（FOCE）interaction method and a mixed error model.The main covariate of 5-FU clearance was body surface area（BSA).Conversely，impact of DPD status on 5-FU elimination was found in a subset of 64% patients.Impact of DPD status was found to be greater than age or sex，which are demographic covariates usually associated with risk of developing toxicities upon 5-FU intake.Conclusion:In patients with DPD-based 5-FU dosing strategy，drug pharmacokinetics becomes linear as saturation of DPD-mediated catabolic pathway is prevented by the preliminary identification of deficient patients.When the DPD issue is addressed preliminary，BSA is a relevant covariate to adjust 5-FU dosage. |
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| Keywords: | popupation pharmacokinetics dihydropyrimidine dehydrogenase（DPD） head and neck cancer NONMEM analysis |
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