title: Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid-Dependent Idiopathic Nephrotic Syndrome.
abstract: Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid-dependent nephrotic syndrome.
  
  
  
  This was a retrospective multicenter study including 95 children with steroid-dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model.
  
  
  
  In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30-60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89;P=0.01).
  
  
  
  Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid-dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population.
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Tellier
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Dallocchio
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Guigonis
authors.affiliation: Service de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire de Limoges, Limoges, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Saint-Marcoux
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest et Centre d'Investigation Clinique, Centre d'Investigation Clinique 1401, INSERM, and.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Llanas
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Ichay
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Flavio
authors.initials: F
authors.lastname: Bandin
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest et Centre d'Investigation Clinique, Centre d'Investigation Clinique 1401, INSERM, and.
authors.forename: Astrid
authors.initials: A
authors.lastname: Godron
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Morin
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Karine
authors.initials: K
authors.lastname: Brochard
authors.affiliation: Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Gandia
authors.affiliation: Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bouchet
authors.affiliation: Service de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire de Limoges, Limoges, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.affiliation: Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest et Centre d'Investigation Clinique, Centre d'Investigation Clinique 1401, INSERM, and.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Harambat
mesh_terms: D019540:Area Under Curve; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D011241:Prednisone / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D005938:Glucocorticoids; D007155:Immunologic Factors; D009173:Mycophenolic Acid; D011241:Prednisone
keywords: Area Under Curve; Drug Monitoring; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pharmacokinetics; Prednisone; Recurrence; children; mycophenolate mofetil; nephrotic syndrome