Department of Pharmacy, First Affiliated Hospital, Harbin Medical University, Harbin, China.
School of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Expert Rev Clin Pharmacol. 2021 Sep;14(9):1173-1182. doi: 10.1080/17512433.2021.1938549. Epub 2021 Jun 28.
: Arsenic trioxide (ATO) was successfully applied to treat acute promyelocytic leukemia (APL).: Inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethyarsinic acid (DMA) in plasma of 143 APL patients with different renal function were determined. Arsenic methylation capacity was evaluated by iAs%, MMA%, DMA%, primary methylation index (PMI, MMA/iAs), and secondary methylated index (SMI, DMA/MMA). Arsenic accumulation with administration frequency were explored. Moreover, safety assessments were performed.: Compared with normal renal function, MMA and DMA concentrations increased 1.5-4 fold in moderate and severe renal impairment groups, iAs increased 1.3-1.7 fold. APL patients with renal impairment showed lower iAs%, but higher DMA% and PMI in plasma than those with normal renal function ( < 0.05). MMA, DMA, and tAs apparently accumulated with administration frequency in moderate and severe renal dysfunction groups. The incidence of QTc interval prolongation and liver injury increased with the increasing severity of renal impairment.: Renal dysfunction may increase exposure to arsenic and arsenic accumulation and affect methylation capacity, then the clinical safety in APL patients treated with ATO. Arsenic-level monitoring and dosing regimen adjustment should be considered in APL patients with moderate and severe renal dysfunction.
三氧化二砷（ATO）成功地应用于治疗急性早幼粒细胞白血病（APL）。我们测定了 143 例不同肾功能 APL 患者血浆中的无机砷（iAs）、一甲基砷酸（MMA）和二甲基砷酸（DMA），通过 iAs%、MMA%、DMA%、初级甲基化指数（PMI，MMA/iAs）和次级甲基化指数（SMI，DMA/MMA）评估砷的甲基化能力。此外，我们还探索了砷的蓄积与给药频率的关系，并进行了安全性评估。与肾功能正常组相比，中重度肾功能损害组 MMA 和 DMA 浓度增加 1.5-4 倍，iAs 增加 1.3-1.7 倍。与肾功能正常组相比，肾功能损害的 APL 患者血浆中 iAs%降低，但 DMA%和 PMI 升高（<0.05）。中重度肾功能障碍组 MMA、DMA 和总砷（tAs）随给药频率明显蓄积。随着肾功能损害程度的加重，QTc 间期延长和肝损伤的发生率增加。肾功能障碍可能会增加砷的暴露和砷的蓄积，影响甲基化能力，从而影响 ATO 治疗 APL 患者的临床安全性。对于中重度肾功能障碍的 APL 患者，应考虑进行砷水平监测和剂量调整。
