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Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria

Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual...

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Autores principales: de Kock, Miné, Tarning, Joel, Workman, Lesley, Allen, Elizabeth N., Tekete, Mamadou M., Djimde, Abdoulaye A., Bell, David J., Ward, Steve A., Barnes, Karen I., Denti, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923181/
https://www.ncbi.nlm.nih.gov/pubmed/29463542
http://dx.doi.org/10.1128/AAC.01370-17
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author de Kock, Miné
Tarning, Joel
Workman, Lesley
Allen, Elizabeth N.
Tekete, Mamadou M.
Djimde, Abdoulaye A.
Bell, David J.
Ward, Steve A.
Barnes, Karen I.
Denti, Paolo
author_facet de Kock, Miné
Tarning, Joel
Workman, Lesley
Allen, Elizabeth N.
Tekete, Mamadou M.
Djimde, Abdoulaye A.
Bell, David J.
Ward, Steve A.
Barnes, Karen I.
Denti, Paolo
author_sort de Kock, Miné
collection PubMed
description Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below −2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult.
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spelling pubmed-59231812018-05-11 Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria de Kock, Miné Tarning, Joel Workman, Lesley Allen, Elizabeth N. Tekete, Mamadou M. Djimde, Abdoulaye A. Bell, David J. Ward, Steve A. Barnes, Karen I. Denti, Paolo Antimicrob Agents Chemother Pharmacology Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below −2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult. American Society for Microbiology 2018-04-26 /pmc/articles/PMC5923181/ /pubmed/29463542 http://dx.doi.org/10.1128/AAC.01370-17 Text en Copyright © 2018 de Kock et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Pharmacology
de Kock, Miné
Tarning, Joel
Workman, Lesley
Allen, Elizabeth N.
Tekete, Mamadou M.
Djimde, Abdoulaye A.
Bell, David J.
Ward, Steve A.
Barnes, Karen I.
Denti, Paolo
Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title_full Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title_fullStr Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title_full_unstemmed Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title_short Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria
title_sort population pharmacokinetic properties of sulfadoxine and pyrimethamine: a pooled analysis to inform optimal dosing in african children with uncomplicated malaria
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923181/
https://www.ncbi.nlm.nih.gov/pubmed/29463542
http://dx.doi.org/10.1128/AAC.01370-17
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