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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.

Original publication

DOI

10.1007/s00228-006-0118-y

Type

Journal article

Journal

Eur J Clin Pharmacol

Publication Date

05/2006

Volume

62

Pages

367 - 371

Keywords

Acute Disease, Adolescent, Adult, Analysis of Variance, Antimalarials, Artemisinins, Artesunate, Atovaquone, Drug Combinations, Drug Resistance, Multiple, Drug Therapy, Combination, Female, Half-Life, Humans, Malaria, Falciparum, Pregnancy, Pregnancy Complications, Parasitic, Pregnancy Outcome, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Proguanil, Sesquiterpenes, Thailand