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Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus

The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)((0-12)) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therap...

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Autores principales: Prabha, R., Mathew, B. S., Jeyaseelan, V., Kumar, T. S., Agarwal, I., Fleming, D. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131378/
https://www.ncbi.nlm.nih.gov/pubmed/27942171
http://dx.doi.org/10.4103/0971-4065.174242
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author Prabha, R.
Mathew, B. S.
Jeyaseelan, V.
Kumar, T. S.
Agarwal, I.
Fleming, D. H.
author_facet Prabha, R.
Mathew, B. S.
Jeyaseelan, V.
Kumar, T. S.
Agarwal, I.
Fleming, D. H.
author_sort Prabha, R.
collection PubMed
description The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)((0-12)) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therapeutic drug monitoring of MPA. On the day of the test, 10 specimens were collected, analyzed, and MPA AUC((0-12)) was calculated. Using step-wise regression analysis, LSS equations were developed. Using bootstrap validation, the predictive performance was calculated. The measured mean (standard deviation) for the trough concentration and AUC((0-12)) were 2.55 (1.57) μg/ml and 62.6 (21.67) mg.h/L, respectively. The range of trough concentrations and AUC((0-12)) were 0.7–5.54 μg/ml and 22.1–104.8 mg.h/L, respectively. The interindividual variability (%CV) for dose normalized AUC((0-12)) and dose normalized C(trough) was 46.5% and 61.1%, respectively. The correlation between the concentrations at the different time points and MPA AUC((0-12)) ranged from 0.05 (1.5 h) to 0.56 (4 h). Two LSS equations that included 4 or 5 time points up to 3 h were developed and validated. The 4 point LSS had a correlation (R(2)) of 0.88 and the 5 point LSS an R(2) of 0.87. With respect to the 4 point and 5 point MPA LSS AUC((0-12)), the bias was 1.92% and 1.96%, respectively, and the imprecision was 11.24% and 11.28%, respectively. A 4 point LSS which concludes within 3 h after the administration of the MMF dose was developed and validated, to determine the MPA AUC((0-12)) in children with SLE.
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spelling pubmed-51313782016-12-09 Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus Prabha, R. Mathew, B. S. Jeyaseelan, V. Kumar, T. S. Agarwal, I. Fleming, D. H. Indian J Nephrol Original Article The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)((0-12)) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therapeutic drug monitoring of MPA. On the day of the test, 10 specimens were collected, analyzed, and MPA AUC((0-12)) was calculated. Using step-wise regression analysis, LSS equations were developed. Using bootstrap validation, the predictive performance was calculated. The measured mean (standard deviation) for the trough concentration and AUC((0-12)) were 2.55 (1.57) μg/ml and 62.6 (21.67) mg.h/L, respectively. The range of trough concentrations and AUC((0-12)) were 0.7–5.54 μg/ml and 22.1–104.8 mg.h/L, respectively. The interindividual variability (%CV) for dose normalized AUC((0-12)) and dose normalized C(trough) was 46.5% and 61.1%, respectively. The correlation between the concentrations at the different time points and MPA AUC((0-12)) ranged from 0.05 (1.5 h) to 0.56 (4 h). Two LSS equations that included 4 or 5 time points up to 3 h were developed and validated. The 4 point LSS had a correlation (R(2)) of 0.88 and the 5 point LSS an R(2) of 0.87. With respect to the 4 point and 5 point MPA LSS AUC((0-12)), the bias was 1.92% and 1.96%, respectively, and the imprecision was 11.24% and 11.28%, respectively. A 4 point LSS which concludes within 3 h after the administration of the MMF dose was developed and validated, to determine the MPA AUC((0-12)) in children with SLE. Medknow Publications & Media Pvt Ltd 2016 /pmc/articles/PMC5131378/ /pubmed/27942171 http://dx.doi.org/10.4103/0971-4065.174242 Text en Copyright: © Indian Journal of Nephrology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Prabha, R.
Mathew, B. S.
Jeyaseelan, V.
Kumar, T. S.
Agarwal, I.
Fleming, D. H.
Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title_full Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title_fullStr Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title_full_unstemmed Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title_short Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
title_sort development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131378/
https://www.ncbi.nlm.nih.gov/pubmed/27942171
http://dx.doi.org/10.4103/0971-4065.174242
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