基于药代动力学特点的肿瘤大剂量维生素C临床增效策略  

Pharmacokinetic characteristics and clinical synergistic strategy of high-dose vitamin C against cancer

作　　者：王诗婉 王欣 曲晋秀 何嘉 赵媛 饶本强 Wang Shiwan;Wang Xin;Qu Jinxiu;He Jia;Zhao Yuan;Rao Benqiang(Center for Oncology Nutrition and Metabolism,Beijing Shijitan Hospital,Capital Medical Univerisity/Key Laboratory of Cancer FSMP for State Market Regulation,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院肿瘤营养与代谢中心,国家肿瘤市场监管重点实验室,北京100038

出　　处：《肿瘤代谢与营养电子杂志》2024年第2期270-275,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家自然科学基金(82074061);国家重点研发计划项目(2022YFC2009601)。

摘　　要：肿瘤大剂量维生素C(HDVC)治疗在临床前实验中对化疗、放疗、靶向治疗等具有协同或增敏效果。然而,HDVC临床疗效有限,对于肿瘤患者预后无明显改善作用。这可能与以下3个药代动力学特点有关:维生素C半衰期仅30 min,易变性;经肾一级动力学消除,排泄快,有效浓度持续时间仅数小时;易被机体抗氧化物系统(特别是还原型谷胱甘肽)代谢。停止输注后血浆维生素C浓度快速下降,导致药物峰浓度或有效浓度持续时间不足以杀灭体内肿瘤细胞。HDVC作为一种廉价、低毒的抗肿瘤疗法,寻找增效策略是实现其临床转化的突破点,本文从现有的临床试验中归纳HDVC临床增效策略,包括调整溶媒,首选灭菌水配制,现用现配,真空密封处理;统一化给药剂量、标准化给药方案,推荐单次剂量75~100 g(1.5~2.2 g/kg)以1 g/min经静脉定速滴注,每周至少3次,达到4周或更长;使用纳米技术提高转运效率;联合用药,如联合三氧化二砷或FOLFOX方案等,可通过提高血药浓度、延长有效浓度持续时间、延缓药物代谢3种机制提升HDVC临床疗效,为后续HDVC规范化临床应用提供思路和依据。High-dose vitamin C(HDVC)therapy has synergistic or sensitizing effects on chemotherapy,radiotherapy,and targeted therapy in preclinical experiments.However,the clinical efficacy of HDVC is limited,which shows that there is no significant improvement in the prognosis of cancer patients.This may be related to the pharmacokinetic characteristics of vitamin C,such as Vitamin C is volatile that its half-life is only 30 minutes,and is rapidly excreted through renal first-order kinetics,also its effective concentration duration of only a few hours.Thus,after stopping infusion,the plasma vitamin C concentration rapidly decreases,resulting in insufficient time for the drug to reach a peak concentration or maintain an effective concentration to kill tumor cells in the body.As a cheap and low-toxicity anti-tumor therapy,HDVC needs to find strategies to enhance its clinical efficacy.This article summarizes the clinical efficacy enhancement strategies of HDVC from existing clinical trials by increasing blood concentrations,prolonging effective concentration durations,and delaying drug metabolism,which including adjusting the solvent,using sterile water as the preferred preparation,preparing it on site and sealing it with vacuum,standardizing the dosing schedule,and recommending a single dose of 75-100 g(1.5-2.2 g/kg)administered intravenously at a constant speed of 1g/min for at least 3 times per week for 4 weeks or longer.Nanotechnology and combining with arsenic trioxide or FOLFOX can also enhance the clinical efficacy of HDVC.These strategies provide ideas and references for the standardized clinical application of HDVC in the future.

关 键 词：维生素C 抗肿瘤 临床疗效 药代动力学 

分 类 号：R969[医药卫生—药理学]