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Multicenter Study
. 2016 Oct 7;11(10):1777-1782.
doi: 10.2215/CJN.00320116. Epub 2016 Jul 21.

Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid-Dependent Idiopathic Nephrotic Syndrome

Stéphanie Tellier  1 , Aymeric Dallocchio  1 , Vincent Guigonis  1 , Frank Saint-Marcoux  2 , Brigitte Llanas  3 , Lydia Ichay  4 , Flavio Bandin  1 , Astrid Godron  3 , Denis Morin  4 , Karine Brochard  1 , Peggy Gandia  5 , Stéphane Bouchet  6 , Pierre Marquet  2 , Stéphane Decramer  1 , Jérôme Harambat  3
Affiliations
Multicenter Study

Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid-Dependent Idiopathic Nephrotic Syndrome

Stéphanie Tellier et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Results: 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).

Conclusions: 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.

Keywords: Area Under Curve; Drug Monitoring; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pharmacokinetics; Prednisone; Recurrence; children; mycophenolate mofetil; nephrotic syndrome.

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Figures

Figure 1.
Figure 1.
Area under the concentration-time curve of mycophenolic acid (MPA-AUC) values in relapsers and nonrelapsers in patients with idiopathic nephrotic syndrome (n=140 MPA-AUC in 95 patients). Box and whiskers plots show minimums, medians, 25th percentiles, medians, 75th percentiles, and maximums.
See this image and copyright information in PMC

References

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