Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery

Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed‐effects modeling to characterize the effects of pregnancy, postpartum...

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Autores principales: de Kock, M, Tarning, J, Workman, L, Nyunt, MM, Adam, I, Barnes, KI, Denti, P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529735/
https://www.ncbi.nlm.nih.gov/pubmed/28597978
http://dx.doi.org/10.1002/psp4.12181
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author de Kock, M
Tarning, J
Workman, L
Nyunt, MM
Adam, I
Barnes, KI
Denti, P
author_facet de Kock, M
Tarning, J
Workman, L
Nyunt, MM
Adam, I
Barnes, KI
Denti, P
author_sort de Kock, M
collection PubMed
description Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed‐effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3‐fold for sulfadoxine but decreased by 18% for pyrimethamine. Postpartum sulfadoxine clearance decreased gradually over 13 weeks. This finding, together with hematocrit‐based scaling of plasma to whole‐blood concentrations and allometric scaling of pharmacokinetics parameters with body weight, enabled site‐specific differences in the pharmacokinetic profiles to be reduced significantly but not eliminated. Further research is necessary to explain residual site‐specific differences and elucidate whether dose‐optimization, to address the 3‐fold increase in clearance of sulfadoxine in pregnant women, is necessary, viable, and safe with the current fixed dose combination of sulfadoxine/pyrimethamine.
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spelling pubmed-55297352017-08-02 Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery de Kock, M Tarning, J Workman, L Nyunt, MM Adam, I Barnes, KI Denti, P CPT Pharmacometrics Syst Pharmacol Original Articles Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed‐effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3‐fold for sulfadoxine but decreased by 18% for pyrimethamine. Postpartum sulfadoxine clearance decreased gradually over 13 weeks. This finding, together with hematocrit‐based scaling of plasma to whole‐blood concentrations and allometric scaling of pharmacokinetics parameters with body weight, enabled site‐specific differences in the pharmacokinetic profiles to be reduced significantly but not eliminated. Further research is necessary to explain residual site‐specific differences and elucidate whether dose‐optimization, to address the 3‐fold increase in clearance of sulfadoxine in pregnant women, is necessary, viable, and safe with the current fixed dose combination of sulfadoxine/pyrimethamine. John Wiley and Sons Inc. 2017-06-09 2017-07 /pmc/articles/PMC5529735/ /pubmed/28597978 http://dx.doi.org/10.1002/psp4.12181 Text en © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
de Kock, M
Tarning, J
Workman, L
Nyunt, MM
Adam, I
Barnes, KI
Denti, P
Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title_full Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title_fullStr Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title_full_unstemmed Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title_short Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery
title_sort pharmacokinetics of sulfadoxine and pyrimethamine for intermittent preventive treatment of malaria during pregnancy and after delivery
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529735/
https://www.ncbi.nlm.nih.gov/pubmed/28597978
http://dx.doi.org/10.1002/psp4.12181
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