Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Br J Clin Pharmacol. 2021 Oct;87(10):4020-4026. doi: 10.1111/bcp.14804. Epub 2021 Mar 20.
Arsenic speciation in cerebrospinal fluid (CSF) is critical for treatment/prevention of central nervous system (CNS) relapse in acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide (ATO). Previous study showed low total arsenic level in CSF of APL patients. Mannitol infusion was applied to improve blood-brain barrier (BBB) permeability for arsenic. Arsenite (As ), monomethylarsonic acid (MMA ), dimethylarsinic acid (DMA ), and arsenate (As ) in CSF and plasma were analysed by high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). The profile and concentration of arsenic species in CSF from APL patients administered ATO alone and in combination with mannitol were compared. The overall distribution trend of arsenic species in CSF was As , DMA > MMA > As . Arsenicals accumulated in CSF with administration frequency. The permeability of BBB for As was higher than that for MMA and DMA . Arsenic concentration in CSF was much lower than that in plasma. There were significantly higher arsenic species concentrations in CSF of APL patients treated with mannitol than that without mannitol. Mannitol infusion significantly increased As penetration into CSF, which was beneficial to optimize efficacy in APL patients with CNS relapse.
脑脊液（CSF）中的砷形态对于用三氧化二砷（ATO）治疗的急性早幼粒细胞白血病（APL）患者中枢神经系统（CNS）复发的治疗/预防至关重要。先前的研究表明 APL 患者 CSF 中的总砷水平较低。应用甘露醇输注以提高血脑屏障（BBB）对砷的通透性。采用高效液相色谱-氢化物发生-原子荧光光谱法（HPLC-HG-AFS）分析 CSF 和血浆中的砷形态，包括亚砷酸盐（As ）、一甲基砷酸（MMA）、二甲基砷酸（DMA）和砷酸盐（As ）。比较了单独使用 ATO 以及与甘露醇联合使用时 APL 患者 CSF 中砷形态的特征和浓度。CSF 中砷形态的总体分布趋势为 As 、DMA > MMA > As 。随着给药频率的增加，砷剂在 CSF 中积累。BBB 对 As 的通透性高于 MMA 和 DMA。CSF 中的砷浓度远低于血浆中的浓度。与未使用甘露醇的患者相比，使用甘露醇治疗的 APL 患者 CSF 中的砷形态浓度明显更高。甘露醇输注显著增加了 As 向 CSF 的渗透，这有利于优化 CNS 复发的 APL 患者的疗效。
