title: Pharmacokinetic properties of artemether, dihydroartemisinin, lumefantrine, and quinine in pregnant women with uncomplicated plasmodium falciparum malaria in Uganda.
abstract: Pregnancy alters the pharmacokinetic properties of many drugs used in the treatment of malaria, usually resulting in lower drug exposures. This increases the risks of treatment failure, adverse outcomes for the fetus, and the development of resistance. The pharmacokinetic properties of artemether and its principal metabolite dihydroartemisinin (n = 21), quinine (n = 21), and lumefantrine (n = 26) in pregnant Ugandan women were studied. Lumefantrine pharmacokinetics in a nonpregnant control group (n = 17) were also studied. Frequently sampled patient data were evaluated with noncompartmental analysis. No significant correlation was observed between estimated gestational age and artemether, dihydroartemisinin, lumefantrine, or quinine exposures. Artemether/dihydroartemisinin and quinine exposures were generally low in these pregnant women compared to values reported previously for nonpregnant patients. Median day 7 lumefantrine concentrations were 488 (range, 30.7 to 3,550) ng/ml in pregnant women compared to 720 (339 to 2,150) ng/ml in nonpregnant women (P = 0.128). There was no statistical difference in total lumefantrine exposure or maximum concentration. More studies with appropriate control groups in larger series are needed to characterize the degree to which pregnant women are underdosed with current antimalarial dosing regimens.
authors.affiliation: Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
authors.forename: Frank
authors.initials: F
authors.lastname: Kloprogge
authors.forename: Mehul
authors.initials: M
authors.lastname: Dhorda
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Guerin
authors.forename: Patrice
authors.initials: P
authors.lastname: Piola
mesh_terms: D000293:Adolescent; D000328:Adult; D000077549:Artemether; D037621:Artemisinins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004983:Ethanolamines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy; D011247:Pregnancy; D011803:Quinine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C039060:artenimol; D011803:Quinine; D000077549:Artemether; D000078102:Lumefantrine
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