European Journal of Clinical Pharmacology

, Volume 62, Issue 5, pp 367–371

Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria

  • R. McGready
  • K. Stepniewska
  • S. A. Ward
  • T. Cho
  • G. Gilveray
  • S. Looareesuwan
  • N. J. White
  • F. Nosten
Pharmacokinetics and Disposition

DOI: 10.1007/s00228-006-0118-y

Cite this article as:
McGready, R., Stepniewska, K., Ward, S.A. et al. Eur J Clin Pharmacol (2006) 62: 367. doi:10.1007/s00228-006-0118-y

Abstract

Objective

To determine the pharmacokinetic properties of dihydroartemisinin (DHA) following oral artesunate treatment in women with recrudescent multi-drug resistant falciparum malaria, in the second and third trimesters of pregnancy.

Methods

Serial plasma concentrations of artesunate and DHA were measured in 24 women after the final dose of a 3 day treatment with artesunate (4 mg kg−1 day−1) and atovaquone (20 mg kg−1 day−1) plus proguanil (8 mg kg−1 day−1), daily. Conventional non-compartmental modelling and a population one-compartment pharmacokinetic model were applied to the data.

Results

Artesunate was very rapidly eliminated. For DHA the median [90% range] estimate of oral clearance (CI/F) was 4.0 [0.8–20.7] l hour−1 kg−1, total apparent volume of distribution (Vd/f) was 3.4 [0.9–60.7] l/kg, and terminal elimination half-life was 1.0 [0.6–2.4] h.

Conclusion

The kinetics of DHA are modified by pregnancy. The plasma levels of the active antimalarial metabolite DHA are lower than reported previously in non-pregnant adults. Dose-optimisation studies in pregnant women are needed.

Keywords

MalariaPlasmodium falciparumArtesunateDHAPharmacokineticsPregnancy

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • R. McGready
    • 1
    • 2
    • 3
  • K. Stepniewska
    • 2
    • 3
  • S. A. Ward
    • 4
  • T. Cho
    • 1
  • G. Gilveray
    • 1
  • S. Looareesuwan
    • 2
  • N. J. White
    • 2
    • 3
  • F. Nosten
    • 1
    • 2
    • 3
  1. 1.Shoklo Malaria Research UnitMae SotThailand
  2. 2.Faculty of Tropical MedicineMahidol UniversityBangkokThailand
  3. 3.Centre for Tropical Medicine and VaccinologyChurchill HospitalHeadingtonUK
  4. 4.Molecular and Biochemical ParasitologyLiverpool School of Tropical MedicinePembroke PlaceUK