1. ¹Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
2. ²Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
3. ³Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
4. ⁴Department of Obstetrics and Gynaecology, University of Khartoum, Khartoum, Sudan
5. ⁵Malaria Research & Training Center, University of Bamako, Bamako, Mali
6. ⁶Malaria Institute at Macha, Macha, Zambia
7. ⁷Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
8. ⁸Maputo Provincial Department of Health, Maputo, Mozambique
9. ⁹Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

Correspondence: MM Nyunt, (mnyunt@jhsph.edu); KI Barnes, (karen.barnes@uct.ac.za)

Received 2 June 2009; Accepted 27 July 2009; Published online 23 September 2009.

Abstract

Malaria during pregnancy is associated with maternal and fetal morbidity and mortality. In order to minimize the burden, sulfadoxine–pyrimethamine (SP) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy (IPTp). However, only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy. We conducted a prospective, self-matched, multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics. After adjusting for the effects of potential confounders, blood concentrations (associated with therapeutic efficacy) of pyrimethamine were higher (geometric mean ratio (GMR) 1.33; 95% confidence interval (CI) 1.18–1.51; P < 0.001) and those of sulfadoxine were lower (GMR 0.91; 95% CI 0.84–0.98; P = 0.013) on day 7 after SP administration during pregnancy than after the postpartum period. SP pharmacokinetic parameters differed significantly among the study sites. Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites, it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings.