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Characteristics of arsenic species in cerebrospinal fluid (CSF) of acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide plus mannitol
Author(s) -
Guo Meihua,
Zhao Qilei,
Fan Shengjin,
Wu Zhiqiang,
Lin Liwang,
Chen Hongzhu,
Gao Yanhui,
Hai Xin
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14804
Subject(s) - arsenic trioxide , arsenic , mannitol , arsenate , chemistry , arsenite , cerebrospinal fluid , acute promyelocytic leukemia , pharmacology , chromatography , biochemistry , medicine , organic chemistry , retinoic acid , gene
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 III ), monomethylarsonic acid (MMA V ), dimethylarsinic acid (DMA V ), and arsenate (As V ) 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 III , DMA V > MMA V > As V . Arsenicals accumulated in CSF with administration frequency. The permeability of BBB for As III was higher than that for MMA V and DMA V . 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 III penetration into CSF, which was beneficial to optimize efficacy in APL patients with CNS relapse.