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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • de Kock, M; Tarning, J; Workman, L; Nyunt, MM; Adam, I; Barnes, KI; Denti, P

Published Date

  • July 2017

Published In

Volume / Issue

  • 6 / 7

Start / End Page

  • 430 - 438

PubMed ID

  • 28597978

Pubmed Central ID

  • 28597978

Electronic International Standard Serial Number (EISSN)

  • 2163-8306

Digital Object Identifier (DOI)

  • 10.1002/psp4.12181

Language

  • eng

Conference Location

  • United States