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Penetrations Of Methylprednisolone Sodium Succinate,Cyclophosphamide And Methotrexate Across The Blood-brain Barrier Of Patients With Neuropsychiatric Systemic Lupus Erythematosus

Posted on:2013-07-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:H LuFull Text:PDF
GTID:1264330401456103Subject:Clinical Medicine
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BackgroundOne 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.ObejectiveThis study was aimed to explore penetrations of Methylprednisolone Sodium Succinate, Cyclophosphamide and Methotrexate across the blood-brain barrier in patients with NPSLE.MethodsCase-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.ResultsIn 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%.ConclusionsIn 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.
Keywords/Search Tags:Neuropsychiatric systemic lupus erythematosus, Methylprednisolone Sodium Succinate, Cyclophosphamide, Methotrexate, UPLC-MS/MS
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