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Pre‐dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases
Author(s) -
Streicher Caroline,
Djabarouti Sarah,
Xuereb Fabien,
Lazaro Estibaliz,
Legeron Rachel,
Bouchet Stéphane,
Greib Carine,
Breilh Dominique,
Pellegrin JeanLuc,
Viallard JeanFrançois
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12462
Subject(s) - mycophenolic acid , mycophenolate , medicine , therapeutic drug monitoring , vasculitis , gastroenterology , receiver operating characteristic , area under the curve , pharmacokinetics , autoimmune disease , cohort , disease , transplantation
Aim To date, neither the benefit of mycophenolic acid ( MPA ) therapeutic drug monitoring ( TDM ), the prodrug of mycophenolate mofetil ( MMF ), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus ( SLE ) or vasculitis. Methods MPA areas under the concentration–time curves between 0 and 12 h, 12 h trough concentrations and pre‐dose concentrations ( C 0 ) were determined for 23 patients with SLE and 21 with systemic vasculitis. The relationship between patients' pharmacokinetic ( PK ) variables and their clinical outcomes during follow‐up were analyzed. Results In both autoimmune diseases, at PK assessment, median MPA C 0 for patients with uncontrolled disease was significantly lower than that of patients with stable disease or in remission, 1.6 mg l –1 ( IQR 0.9–2.1 mg l –1 ) vs. 2.95 mg l –1 ( IQR 1.38–3.73 mg l –1 ) for SLE ( P = 0.048) and 1.55 mg l –1 ( IQR 0.98–2.18 mg l –1 ) vs. 3 mg l –1 ( IQR 2.2–4.4 mg l –1 ) for vasculitis ( P = 0.016). According to our receiver operating characteristics curve analysis, a C 0 threshold of 2.5–3 mg l –1 was best able to discriminate a flare ( SLE : 88% sensitivity, 80% specificity; vasculitis: 100% sensitivity, 90% specificity). Patients with C 0 ≥ 2.5–3 mg l –1 at inclusion had better clinical outcomes during the 12 months following PK assessment. Conclusion Provided that the benefit of TDM in patients with autoimmune diseases could be confirmed by randomized, controlled trials, it might be based on the C 0 measured approximately 12 h post‐dose.