摘要
研究背景
外周给药治疗神经精神狼疮(Neuropsychiatric Systemic Lupus Erythematosus, NPSLE)的原理之一是药物在脑脊液中的浓度高于最小有效治疗浓度,外周给药若不能较好地穿透血脑屏障,就必须依赖于鞘内注射这些药物。目前,尚不能明确NPSLE患者中各药物穿透血脑屏障的能力。
研究目的
本研究旨在探索NPSLE患者使用甲泼尼龙琥珀酸钠(Methylprednisolone Sodium Succinate, MPSS).环磷酰胺(Cyclophosphamide, CP)和甲氨蝶呤(Methotrexate, MTX)后,其穿透血脑屏障的能力。
研究方法
病例纳入标准：1)参考1999年美国风湿学会(American College of Rheumatology, ACR)关于NPSLE的命名和定义的分类标准,结合临床、影像学、脑电图、脑脊液检查等确诊为NPSLE的患者。[1]2)这些患者正在接受MPSS静脉滴注、CP静脉滴注和MTX口服这三种治疗方式的其中一种或多种。
依据文献中这三种药物在血浆和脑脊液中的达峰时间设定标本采集时间,按照时间点分别采集静脉血浆标本和脑脊液标本。建立超高效液相色谱／质谱串联(Ultra Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry, UPLC-MS/MS)定量方法测定各标本中MPSS、CP和MTX的浓度。
结果
本研究各收集了14例MPSS、10例CP和11例MTX样本,MPSS穿透血脑屏障的比率为0.52%±0.30%,CP穿透血脑屏障的比率为22.74%±7.42%,MTX穿透血脑屏障的比率为0.18%±0.48%。
结论
在NPSLE患者中,MPSS和MTX穿透血脑屏障的能力微弱,证明临床上采用鞘内注射地塞米松和MTX的治疗方式是合理的；CP穿透血脑屏障的能力相对较高,静脉用药也可在中枢神经系统局部发挥药效。
Background
One principle of peripheral administrations of drugs in the treatment of neuropsychiatric lupus erythematosus is that the concentrations of these drugs are higher than the minimum effective therapeutic concentrations in the cerebrospinal fluid. If drugs via peripheral administrations can not penetrate the blood-brain barrier, intrathecal injection of these drugs are required. Currently, penetrations of drugs across the blood-brain barrier are not yet clear in patients with NPSLE.
Obejective
This study was aimed to explore penetrations of Methylprednisolone Sodium Succinate, Cyclophosphamide and Methotrexate across the blood-brain barrier in patients with NPSLE.
Methods
Case-inclusion criteria:1) Patients were diagnosed for NPSLE referring to American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes in1999combined with clinical syndromes, imaging, electroencephalography, and cerebrospinal fluid examinations.[1]2) These patients were receiving the treatments of MPSS, CP or/and MTX. Plasma and cerebrospinal fluid samples were collected according to the peak time of these three drugs in plasma and cerebrospinal fluid. Ultra-high performance liquid chromatography/mass spectrometry method was established in order to detect the concentrations of MPSS, CP and MTX in all these samples.
Results
In this study,14MPSS samples,10CP samples and11MTX samples were collected. The penetrating ratio of MPSS across the blood-brain barrier is0.52%±0.30%, the ratio of CP is22.74%±7.42%and the ratio of MTX is0.18%±0.48%.
Conclusions
In patients with NPSLE, the penetrations of MPSS and MTX across the blood-brain barrier are rare, which provides an evidence for intrathecal injection of dexamethasone and MTX clinically. While, the penetration of CP is relatively high, which means that intravenous administration of CP can also have an effect on the central nervous system.
引文
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