Chemotherapy Center, Zhejiang Province Cancer Hospital, 1 Banshandong Road, Gongshu District, Hangzhou, 310012, PR China.
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, 1 Banshandong Road, Gongshu District, Hangzhou, 310012, PR China.
Regul Toxicol Pharmacol. 2018 Oct;98:24-30. doi: 10.1016/j.yrtph.2018.07.001. Epub 2018 Jul 6.
Chidamide is a new subtype-selective histone deacetylase inhibitor (HDACi), which has been approved for the treatment of recurrent or refractory peripheral T-cell lymphoma (PTCL) in China. However, there are few studies about the application of chidamide in PTCL with central nervous system (CNS) involvement. It is essential to investigate the penetration of chidamide in the blood brain barrier (BBB). LC-MS methods were established firstly to determine the concentration of chidamide in rat plasma and CSF. Then five rats were anaesthetized and the plasma and CSF samples were collected at the time of 5, 15, 30, 60, 120, 180, 240, 360 and 480 min after being administered 1 mg/kg chidamide by intravenous injection, respectively. All samples were analyzed with the established LC-MS method by using the precursor/product transitions (m/z) of 391.1/265.1 for chidamide and 441.1/138.2 for internal standard (IS). The PK parameters were calculated after both of the concentrations of chidamide in plasma and CSF were determined. The penetration ratio of chidamide in BBB ranged from 0.19% to 0.67%. Result indicated chidamide could pass through the BBB, enter into the CNS and have the potential to be utilized in PTCL with CNS involvement.
西达本胺是一种新型的组织亚型选择性组蛋白去乙酰化酶抑制剂（HDACi），已在中国被批准用于治疗复发性或难治性外周 T 细胞淋巴瘤（PTCL）。然而，关于西达本胺在伴有中枢神经系统（CNS）受累的 PTCL 中的应用研究较少。研究西达本胺透过血脑屏障（BBB）的能力至关重要。首先建立了 LC-MS 方法来测定大鼠血浆和 CSF 中西达本胺的浓度。然后，在静脉注射 1mg/kg 西达本胺后，将 5 只大鼠麻醉，并分别在 5、15、30、60、120、180、240、360 和 480min 时采集血浆和 CSF 样本。使用建立的 LC-MS 方法，通过西达本胺的前体/产物转换（m/z）391.1/265.1 和内标（IS）的 441.1/138.2 对所有样本进行分析。在确定了血浆和 CSF 中西达本胺的浓度后，计算了 PK 参数。西达本胺在 BBB 中的穿透率范围为 0.19%至 0.67%。结果表明，西达本胺可以透过 BBB，进入 CNS，并有潜力用于伴有 CNS 受累的 PTCL。
