Study On Blood-brain Barrier Permeability Of Methylprednisolone, Cyclophosphamide And Methotrexate In Patients With Neuropsychiatric Lupus

Background:Neuropsychiatric manifestations are commonly recognized in patients with systemic lupus erythematosus and have caused considerable morbidity and mortality. Current guideline for medication treatment of NPSLE includes systemic Methylprednisone Succinate Sodium, Cyclophosphamide and Methotrexate. However, there have been few reports about their cerebrospinal fluid (CSF) concentration and Blood-Brain Barrier penetration level in NPSLE patients. The aim of this study is to investigate CSF concentration of these medications in Chinese patients with NPSLE.Methods:47patients with NPSLE from Peking Union Medical College Hospital were enrolled, paired CSF and serum drug concentration were measure with Ultra-Performance Liquid Chromatography-Mass Spectrometry at peak drug concentration; CSF:serum concentration ratios were calculated to represent penetration level.Results:CTX showed high penetration level of24.78%±8.91%, while MPSS showed penetration level of0.53%±0.26%and MTX does not pass BBB in most samples. Positive correlation exsist between CSF and serum concentration for MPSS (R=0.9041) and CTX(R=0.6039).Conclusions:In conclusion, with high CSF penetration, intravenous administration of CTX can deliver higher dosage to target tissue, possibly explaining better results than intravenous MPSS observed in previous studies. Low penetration ability of MPSS and MTX justify current treatment methods of high dose MPSS and intrathecal MTX injection in NPSLE patients.