Journal article
Pharmacokinetics of sulfadoxine and pyrimethamine for intermittent preventive treatment of malaria during pregnancy and after delivery
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 141.5KB, Terms of use)
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(Preview, Version of record, pdf, 494.3KB, Terms of use)
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- Publisher copy:
- 10.1002/psp4.12181
Authors
- Publisher:
- Wiley
- Journal:
- CPT: Pharmacometrics and Systems Pharmacology More from this journal
- Volume:
- 6
- Issue:
- 7
- Pages:
- 430–438
- Publication date:
- 2017-06-09
- Acceptance date:
- 2017-01-26
- DOI:
- EISSN:
-
2163-8306
- Language:
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English
- Pubs id:
-
pubs:674990
- UUID:
-
uuid:a317a0c7-ea98-49e4-8b89-7220f229f207
- Local pid:
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pubs:674990
- Source identifiers:
-
674990
- Deposit date:
-
2017-01-31
Terms of use
- Copyright holder:
- de Kock et al.
- Copyright date:
- 2018
- Rights statement:
- © 2018 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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
- Notes:
- An erratum has been published for this record and is available to download from the 'Access Document' section or from the publisher at: https://doi.org/10.1002/psp4.12503
- Licence:
- CC Attribution (CC BY)
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