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The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria

  • Rose McGready
  • Kasia Stepniewska
  • Niklas Lindegardh
  • Elizabeth A. Ashley
  • Yar La
  • Pratap Singhasivanon
  • Nicholas J. White
  • François NostenEmail author
Pharmacokinetics and Disposition

Abstract

Objective

To determine the pharmacokinetic properties of artemether and lumefantrine (AL) in pregnant women with recrudescent uncomplicated multi-drug resistant falciparum malaria.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Artemether Lumefantrine Pregnancy Falciparum malaria 

Notes

Acknowledgements

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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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Rose McGready
    • 1
    • 2
    • 3
  • Kasia Stepniewska
    • 2
    • 3
  • Niklas Lindegardh
    • 2
    • 3
  • Elizabeth A. Ashley
    • 1
    • 2
    • 3
  • Yar La
    • 1
  • Pratap Singhasivanon
    • 2
  • Nicholas J. White
    • 2
    • 3
  • François Nosten
    • 2
    • 3
    • 1
    Email author
  1. 1.Shoklo Malaria Research UnitTakThailand
  2. 2.Faculty of Tropical MedicineMahidol UniversityBangkokThailand
  3. 3.Centre for Vaccinology and Tropical MedicineChurchill HospitalOxfordUK

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