Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya.
BACKGROUND
Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP.


METHODS
Seventeen pregnant HIV(-) women and 16 pregnant HIV(+) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV(-) and 6 HIV(+) postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups.


RESULTS
HIV status did not affect the area under the curve (AUC(0-->infinity)) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P<.001), and the median AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/mL/h, P<.001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics.


CONCLUSIONS
Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.
Green
Michael D
MD
Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. MGreen@cdc.gov
van Eijk
Annemieke M
AM
van Ter Kuile
Feiko O
FO
Ayisi
John G
JG
Parise
Monica E
ME
Kager
Piet A
PA
Nahlen
Bernard L
BL
Steketee
Richard
R
Nettey
Henry
H
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007630:Kenya; D008288:Malaria / Q000517:prevention & control; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011739:Pyrimethamine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine