三氧化二砷血药浓度监测中国专家共识

doi:10.12092/j.issn.1009-2501.2026.02.006

摘要/Abstract

摘要：

三氧化二砷（arsenic trioxide，ATO）作为急性早幼粒细胞白血病（acute promyelocytic leukemia，APL）的一线治疗药物，其临床应用已扩展至多种恶性肿瘤的治疗领域。然而，由于其在体内的活性代谢过程复杂，且存在显著的个体间药动学差异，常导致治疗效果不稳定或毒性反应的发生。血药浓度监测利用多种分析技术测定体内药物暴露水平，是个体化用药的常用技术手段和核心环节。本专家共识基于现有相关文献，探讨ATO治疗中血药浓度监测的适用人群、监测指标、最佳监测时机、特殊人群的监测要点以及检测方法，旨在促进血药浓度监测在ATO临床治疗中的规范化实施，助力精准医疗实践。

关键词: 三氧化二砷, 血药浓度, 个体化用药, 专家共识

Abstract:

Arsenic trioxide (ATO) is not only a first-line therapy for acute promyelocytic leukemia (APL) but also a widely accepted treatment in other malignancies. However, ATO therapy may lead to suboptimal efficacy or toxic reactions due to its complex active metabolites and significant interindividual pharmacokinetic variability. Blood concentration monitoring, which employs various analytical techniques to determine drug exposure levels in vivo, serves as both a fundamental technical approach and a core component of personalized medication. This expert consensus systematically discusses the target population for ATO blood drug monitoring, monitoring indicators, optimal sampling times, monitoring recommendations for special populations, and methodological approaches based on current evidence. The primary objectives are to standardize clinical implementation of blood concentration monitoring in ATO treatment and to advance precision medicine practice.

Key words: arsenic trioxide, blood concentration, personalized medication, expert consensus

中图分类号:

《三氧化二砷血药浓度监测中国专家共识》编写组. 三氧化二砷血药浓度监测中国专家共识[J]. 中国临床药理学与治疗学, 2026, 31(2): 185-195.

Writing team for "Chinese expert consensus on blood drug monitoring for arsenic trioxide". Chinese expert consensus on blood drug monitoring for arsenic trioxide[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(2): 185-195.

图/表 2

参考文献 67

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Rating the quality of evidence	Strength of recommendation
High	Strong recommendation:“recommend”or“not recommend”
Moderate	Week recommendation:“suggest”or“not suggest”
Low	Suggestion in form of expert opinion:“expert suggest”or“expert not suggest”
Very low

Rating the quality of evidence	Strength of recommendation
High	Strong recommendation:“recommend”or“not recommend”
Moderate	Week recommendation:“suggest”or“not suggest”
Low	Suggestion in form of expert opinion:“expert suggest”or“expert not suggest”
Very low

编号	推荐意见	参考文献	系统性综述、荟萃分析、随机对照研究	非随机对照研究、队列研究	病例报告	综述	指南、共识	方法学研究、药动学研究	证据等级	推荐强度
1	推荐对以下使用ATO的人群进行血药浓度监测：（1）初发且未接受过ATO治疗的患者；（2）接受标准剂量治疗后临床疗效不佳的患者；（3）出现与ATO相关毒性反应（如QT间期延长、肝损伤、肾损伤、神经毒性）的患者；（4）治疗前心电图示QT间期延长的患者；（5）与易引起QT间期延长药物合用时（如喹诺酮类、胺碘酮、多潘立酮等）；（6）伴有肝功或肾功异常的患者；（7）疑似出现ATO长期不良反应（如皮肤病变）的患者；（8）特殊人群：儿童及65岁以上老年患者。	[21-33]	[30-31]	[25-26] [28-29]	[23] [32]	[21] [24] [27] [33]	[22]		高	推荐
2	建议监测指标：（1）无机砷（iAs，即As^III+As^V）浓度，条件允许情况下同步监测甲基化代谢产物一甲基砷酸（MMA，即MMA^III+DMA^V）和二甲基砷酸（DMA，即DMA^III+DMA^V）的浓度；（2）总砷浓度；（3）计算初级甲基化指数PMI（MMA/iAs）和次级甲基化指数SMI（DMA/MMA），用于评估患者的砷甲基化代谢能力，并辅助提示毒性发生风险。	[34-39]		[37-39]		[34]			中	建议
3	推荐检测样本：（1）首选血浆，便于标准化检测且与现有临床研究数据具有可比性；（2）全血：可更全面反映药物体内暴露水平，尤其适用于评估长期蓄积风险；（3）尿液：建议收集24 h尿液以评估患者砷排泄效率及代谢能力；治疗周期结束后，可进行随机尿液监测作为长期砷蓄积程度的评价指标。	[39-46]		[39-45]				[46]	高	推荐
4	建议于诱导治疗第7天用药前进行基线浓度监测，之后每3～7 d监测一次，诱导治疗结束后30 d监测ATO蓄积情况；在巩固与维持治疗阶段，建议每1～3个月进行监测；若出现ATO相关毒性反应，应立即采血检测。	[46-52]		[46-47] [49]	[52]			[48][50-51]	中	建议
5	建议监测谷浓度（C_trough），参考浓度范围：血浆iAs：8.1～26.8 μg/L，血浆MMA^V：9.8～21.4 μg/L，血浆DMA^V：9.8～22.8 μg/L，血浆总砷：11.5～89.5 μg/L。	[8] [46] [53-55]	[8]	[53-55]				[46]	中	建议
6	建议以血浆总砷C_trough作为儿童患者应用ATO的监测指标，推荐参考浓度范围为17.25～62.97 μg/L。建议用药后第1，3，7天进行监测，之后根据患者个体情况每隔3～7 d监测一次。	[56-59]		[57-59]				[56]	中	建议
7	对于轻中度肾功能不全患者，可给予常规剂量0.15 mg/kg给药；重度肾功能不全（eGFR<30 mL/min）及透析患者，可考虑减量至0.1 mg/kg或延长给药间隔。建议给药后每3 d检测血和尿砷浓度并密切观察。	[54] [60-65]		[54] [61]	[62-65]			[60]	中	建议
8	建议应用高效液相联用氢化物原子荧光光谱法（HPLC-HG-AFS）或高效液相联用电感耦合等离子体质谱法（HPLC-ICP-MS）。	[42] [66-67]						[42] [66-67]	中	推荐

编号	推荐意见	参考文献	系统性综述、荟萃分析、随机对照研究	非随机对照研究、队列研究	病例报告	综述	指南、共识	方法学研究、药动学研究	证据等级	推荐强度
1	推荐对以下使用ATO的人群进行血药浓度监测：（1）初发且未接受过ATO治疗的患者；（2）接受标准剂量治疗后临床疗效不佳的患者；（3）出现与ATO相关毒性反应（如QT间期延长、肝损伤、肾损伤、神经毒性）的患者；（4）治疗前心电图示QT间期延长的患者；（5）与易引起QT间期延长药物合用时（如喹诺酮类、胺碘酮、多潘立酮等）；（6）伴有肝功或肾功异常的患者；（7）疑似出现ATO长期不良反应（如皮肤病变）的患者；（8）特殊人群：儿童及65岁以上老年患者。	[21-33]	[30-31]	[25-26] [28-29]	[23] [32]	[21] [24] [27] [33]	[22]		高	推荐
2	建议监测指标：（1）无机砷（iAs，即As^III+As^V）浓度，条件允许情况下同步监测甲基化代谢产物一甲基砷酸（MMA，即MMA^III+DMA^V）和二甲基砷酸（DMA，即DMA^III+DMA^V）的浓度；（2）总砷浓度；（3）计算初级甲基化指数PMI（MMA/iAs）和次级甲基化指数SMI（DMA/MMA），用于评估患者的砷甲基化代谢能力，并辅助提示毒性发生风险。	[34-39]		[37-39]		[34]			中	建议
3	推荐检测样本：（1）首选血浆，便于标准化检测且与现有临床研究数据具有可比性；（2）全血：可更全面反映药物体内暴露水平，尤其适用于评估长期蓄积风险；（3）尿液：建议收集24 h尿液以评估患者砷排泄效率及代谢能力；治疗周期结束后，可进行随机尿液监测作为长期砷蓄积程度的评价指标。	[39-46]		[39-45]				[46]	高	推荐
4	建议于诱导治疗第7天用药前进行基线浓度监测，之后每3～7 d监测一次，诱导治疗结束后30 d监测ATO蓄积情况；在巩固与维持治疗阶段，建议每1～3个月进行监测；若出现ATO相关毒性反应，应立即采血检测。	[46-52]		[46-47] [49]	[52]			[48][50-51]	中	建议
5	建议监测谷浓度（C_trough），参考浓度范围：血浆iAs：8.1～26.8 μg/L，血浆MMA^V：9.8～21.4 μg/L，血浆DMA^V：9.8～22.8 μg/L，血浆总砷：11.5～89.5 μg/L。	[8] [46] [53-55]	[8]	[53-55]				[46]	中	建议
6	建议以血浆总砷C_trough作为儿童患者应用ATO的监测指标，推荐参考浓度范围为17.25～62.97 μg/L。建议用药后第1，3，7天进行监测，之后根据患者个体情况每隔3～7 d监测一次。	[56-59]		[57-59]				[56]	中	建议
7	对于轻中度肾功能不全患者，可给予常规剂量0.15 mg/kg给药；重度肾功能不全（eGFR<30 mL/min）及透析患者，可考虑减量至0.1 mg/kg或延长给药间隔。建议给药后每3 d检测血和尿砷浓度并密切观察。	[54] [60-65]		[54] [61]	[62-65]			[60]	中	建议
8	建议应用高效液相联用氢化物原子荧光光谱法（HPLC-HG-AFS）或高效液相联用电感耦合等离子体质谱法（HPLC-ICP-MS）。	[42] [66-67]						[42] [66-67]	中	推荐

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