R. McGreadyK. StepniewskaS. A. WardT. ChoG. GilverayS. LooareesuwanN. J. WhiteF. NostenShoklo Malaria Research UnitMahidol UniversityChurchill HospitalLiverpool School of Tropical Medicine2018-08-202018-08-202006-05-01European Journal of Clinical Pharmacology. Vol.62, No.5 (2006), 367-371003169702-s2.0-33646536090https://repository.li.mahidol.ac.th/handle/20.500.14594/23763Objective: To determine the pharmacokinetic properties of dihydroartemisinin (DHA) following oral artesunate treatment in women with recrudescent multidrug 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-1day-1) and atovaquone (20 mg kg-1day-1) plus proguanil (8 mg kg-1day-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] 1 hour-1kg-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. © Springer-Verlag 2006.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1007/s00228-006-0118-y