steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares an observational cohort study稳态霉酚酸酯药代动力学参数使系统性红斑狼疮的临床预测耀斑一项观察性队列研究.pdfVIP
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steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares an observational cohort study稳态霉酚酸酯药代动力学参数使系统性红斑狼疮的临床预测耀斑一项观察性队列研究
Djabarouti et al. Arthritis Research Therapy 2010, 12:R217
/content/12/6/R217
RESEARCH ARTICLE Open Access
Steady-state mycophenolate mofetil
pharmacokinetic parameters enable prediction
of systemic lupus erythematosus clinical
flares: an observational cohort study
1* 1 2 2 2 2
Sarah Djabarouti , Dominique Breilh , Pierre Duffau , Estibaliz Lazaro , Carine Greib , Olivier Caubet ,
1 2 2
Marie-Claude Saux , Jean-Luc Pellegrin , Jean-François Viallard
Abstract
Introduction: The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics
(PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus
erythematosus (SLE) clinical flares.
Methods: At inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its
glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease
activity was assessed during 6 months of follow-up. Potential relationships between those entry MMF-PK variables
and clinical outcome were analyzed.
Results: MMF controlled disease activity in 17 patients (successes) and failed to do so for 8 others (failures). For
failures and successes, respectively, entry MPA areas under the time-concentration curve between 0 and 12 hours
(AUC0-12 h) (medians: 37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C12 h) (medians:
1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion MPAG/MPA C12 h ratios (medians: 18.7 vs 10.2,
P = 0.02) were significantly higher. According to our receiver operating characteristics curve analysis, MPA C12 h
was best abl
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