The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria
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To determine the pharmacokinetic properties of artemether and lumefantrine (AL) in pregnant women with recrudescent uncomplicated multi-drug resistant falciparum malaria.
Pregnant women who had recurrence of parasitaemia following 7 days supervised quinine treatment were treated with AL. Serial blood samples were taken over a 7-day period, and pharmacokinetic parameters were estimated. For lumefantrine, these data were compared in a population pharmacokinetic model with data from non-pregnant, mainly male adults with acute malaria.
The pregnant women (five in the second trimester and eight in the third trimester) had lower concentrations of artemether, dihydroartemisinin and lumefantrine, and the elimination of lumefantrine in pregnant women was more rapid than reported previously in non-pregnant adults.
Pregnancy is associated with reduced plasma concentrations of both artemether and lumefantrine. This is likely to be of therapeutic significance as plasma concentrations of lumefantrine, after elimination of artemether, are an important determinant of cure. Further studies are needed to determine the optimum dose regimen of artemether-lumefantrine in pregnancy.
KeywordsArtemether Lumefantrine Pregnancy Falciparum malaria
We sincerely thank the pregnant women for their cooperation in completing this study. We thank also the diligent staff from SMRU. The Shoklo Malaria Research Unit is part of the Faculty of Tropical Medicine in Bangkok. This investigation was part of the Wellcome-Trust Mahidol University Oxford Tropical Medicine Research Programme, supported by the Wellcome-Trust of Great Britain. The study was supported by UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR).
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