Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring.

Abstract : AIMS: The use of mycophenolate mofetil (MMF) in children with Systemic Lupus Erythematosus (SLE) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to describe mycophenolic acid (MPA; the active moiety of MMF) pharmacokinetics; (ii) to develop a Bayesian estimator (BE) allowing the determination AUC (Area under the curve) from a limited number of blood samples; and (ii) to explore the relationships between exposure indices to MPA and the clinical status in children with SLE. METHODS: This was a retrospective study including 36 children with SLE, extracted from the expert system ISBA, for whom full- pharmacokinetic profiles of MPA were collected together with clinical data. A pharmacokinetic model and a BE were developed using an iterative two-stage Bayesian approach. ROC curve analyses and logistic regressions was used to investigate the association of exposure and active disease. RESULTS: A pharmacokinetic model and a BE were developed that allowed good AUC estimation performance (bias±SD=-0.02±0.15). ROC curve analyses showed that AUC/dose<0.06 and AUC<44 mg*h/L were associated with a good sensitivity and specificity for active disease (78%/94% and 94%/56% respectively). When introduced in a logistic regression model, AUC<44 mg.h/L and AUC/dose<0.06 were associated with an increased risk of active disease (OR=21.2[2.3-196.1], p=0.007; and OR [95%CI]=59.5[5.9-588.2], p=0.0005 respectively). CONCLUSIONS: The developed pharmacokinetics BE could be used to prospectively test the interest of MPA monitoring for limiting relapse of the disease or its progression.
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British Journal of Clinical Pharmacology, Wiley, 2014, 78 ((4)), pp.867-76. 〈10.1111/bcp.12392〉
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Jean-Baptiste Woillard, Brigitte Bader-Meunier, Rémi Salomon, Bruno Ranchin, Stéphane Decramer, et al.. Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring.. British Journal of Clinical Pharmacology, Wiley, 2014, 78 ((4)), pp.867-76. 〈10.1111/bcp.12392〉. 〈inserm-00966145〉

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