Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria
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- McGready, R., Stepniewska, K., Ward, S.A. et al. Eur J Clin Pharmacol (2006) 62: 367. doi:10.1007/s00228-006-0118-y
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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.
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.
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.
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.