三氧化二砷单药治疗急性早幼粒细胞白血病患者的红细胞中砷形态的时间进程。
Time course of arsenic species in red blood cells of acute promyelocytic leukemia (APL) patients treated with single agent arsenic trioxide.
机构信息
a Department of Pharmacy , The First Affiliated Hospital of Harbin Medical University , Harbin , China.
b Department of Hematology , The First Affiliated Hospital of Harbin Medical University , Harbin , China.
出版信息
Expert Rev Clin Pharmacol. 2019 Apr;12(4):371-378. doi: 10.1080/17512433.2019.1586532. Epub 2019 Mar 11.
BACKGROUND
Arsenic trioxide (ATO) is widely applied to treat acute promyelocytic leukemia (APL). To elucidate metabolism and toxicity of arsenic, we analyzed time course of arsenic species in red blood cells (RBCs) of APL patients.
METHODS
Nine APL patients received ATO (0.16 mg/kg/day) through 18-h infusion. Blood was collected before daily administration (days 2 to 9), and at different time points on day 8. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were detected by HPLC-ICP-MS.
RESULTS
Arsenic species reached C at 18 h on day 8. Arsenicals gradually accumulated during days 2 to 9, whereas their percentages remained almost constant. The general trend in red blood cells (RBCs) was iAs > MMA > DMA. MMA was consistently the predominant methylated arsenic metabolite in RBCs. iAs, MMA, and tAs (tAs = iAs + DMA + MMA) concentrations (P < 0.0001), MMA/DMA ratios (P = 0.0016) and iAs% (P = 0.0013) were higher in RBCs than in plasma.
CONCLUSIONS
Time course of arsenic species reveal kinetic characteristic of ATO metabolites in RBCs. Arsenic species accumulated with administration frequency. Arsenic species in RBCs were remarkably different from those in plasma. Time course of arsenic species in RBCs is important in ATO clinical application.
背景
三氧化二砷（ATO）广泛用于治疗急性早幼粒细胞白血病（APL）。为了阐明砷的代谢和毒性，我们分析了 APL 患者红细胞（RBC）中砷的形态随时间的变化。
方法
9 例 APL 患者接受 ATO（0.16mg/kg/天）18 小时输注。在每日给药前（第 2 至 9 天）和第 8 天的不同时间点采集血液。用 HPLC-ICP-MS 检测无机砷（iAs）、一甲基砷酸（MMA）和二甲基砷酸（DMA）。
结果
砷形态于第 8 天 18 小时达到 C。砷剂在第 2 至 9 天逐渐积累，而其百分率几乎保持不变。红细胞（RBC）中的一般趋势是 iAs > MMA > DMA。MMA 一直是 RBC 中主要的甲基化砷代谢物。iAs、MMA 和总砷（tAs=tAs=iAs+DMA+MMA）浓度（P <0.0001）、MMA/DMA 比值（P =0.0016）和 iAs%（P =0.0013）在 RBC 中均高于血浆。
结论
砷形态的时间过程揭示了 ATO 代谢物在 RBC 中的动力学特征。砷形态随给药频率而积累。RBC 中的砷形态与血浆中的砷形态有显著差异。RBC 中砷形态的时间过程在 ATO 临床应用中非常重要。
Zotero 插件