Pharmacokinetics of sulfadoxine and pyrimethamine in intermittent preventive treatment of malaria in pregnancy.
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.
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. mnyunt@jhsph.edu
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Nyunt
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Adam
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Kayentao
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van Dijk
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Thuma
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Mauff
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Little
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Cassam
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Guirou
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Traore
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Doumbo
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Sullivan
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Smith
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Barnes
D000328:Adult; D000349:Africa; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000401:mortality / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000187:drug effects; D049590:Postpartum Period; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine