Effective plasma concentrations of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in the remission-maintenance phase

• Published in: Journal of clinical pharmacy and therapeutics Vol. 37; no. 2; pp. 217 - 220
• Main Authors: Mino, Y., Naito, T., Shimoyama, K., Ogawa, N., Kawakami, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2012; Blackwell; Hindawi Limited
• Subjects: Adult; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Glucocorticoids - administration & dosage; Glucocorticoids - therapeutic use; Glucuronides - pharmacokinetics; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - physiopathology; Male; Medical sciences; Middle Aged; mycophenolic acid; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; mycophenolic acid phenolic glucuronide; pharmacokinetics; Pharmacology. Drug treatments; Prednisolone - administration & dosage; Prednisolone - therapeutic use; prednisolone dose reduction; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; systemic lupus erythematosus; therapeutic efficacy; Treatment Outcome; Antineoplastic agent; Skin disease; Mycophenolic acid; Phenolic acid; Autoimmune disease; Glucuroconjugate; Systemic lupus erythematosus; Systemic disease; Remission; prednisolone dose reduction; Dose; Prednisolone; Human; Corticosteroid; Immunopathology; Connective tissue disease; Treatment efficiency; Antiinflammatory agent; Immunomodulator; Treatment; Adrenal hormone; therapeutic efficacy; Immunosuppressive agent; Inosine monophosphate dehydrogenase inhibitor; Pharmacokinetics; mycophenolic acid phenolic glucuronide
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2011.01269.x

Summary What is known and Objective:  Mycophenolate mofetil (MMF) has been reported recently to be effective in the treatment of systemic lupus erythematosus (SLE). The therapeutic range of mycophenolic acid (MPA) in SLE in the remission‐maintenance phase remains to be clarified. The aim of this study was to evaluate the therapeutic efficacy of MMF and predose plasma concentrations of MPA and its phenolic glucuronide (MPAG) in patients with SLE in the remission‐maintenance phase. Methods:  Thirty‐one patients with SLE receiving a fixed dosage regimen of MMF (median and interquartile range, 1500 and 1000–2000 mg/day) for at least 1 month and who had not experienced any adverse drug reactions for more than 3 months were enrolled. Results:  Significant improvement was observed after MMF administration in total haemolytic complement CH50 and its fractions C3 and C4, immunoglobulins IgG, IgA and IgM, anti‐dsDNA antibody, serum concentration of albumin and red blood cell count, even though the mean daily dose of prednisolone was significantly reduced (P = 0·02). Median predose plasma concentrations of MPA and MPAG were 1·95 and 26·2 μg/mL (interquartile ranges, 0·94–2·96 and 18·6–53·7 μg/mL). Predose plasma concentrations of MPA and MPAG correlated significantly with MMF dose (r = 0·64, P < 0·01 and r = 0·39, P = 0·03). What is new and Conclusions:  MMF improved clinical laboratory markers and reduced prednisolone dosage in SLE patients with predose plasma concentration of MPA and MPAG in the interquartile ranges of 0·94–2·96 and 18·6–53·7 μg/mL, respectively.