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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Adolescent
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Adult
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Analysis of Variance
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Antimalarials / administration & dosage
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Antimalarials / pharmacokinetics*
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Antimalarials / therapeutic use
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Artemisinins / administration & dosage
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Artemisinins / pharmacokinetics*
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Artemisinins / therapeutic use
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Artesunate
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Atovaquone / administration & dosage
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Atovaquone / pharmacokinetics
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Atovaquone / therapeutic use
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Drug Combinations
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Drug Resistance, Multiple
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Drug Therapy, Combination
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Female
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Half-Life
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Humans
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Malaria, Falciparum / blood
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Malaria, Falciparum / drug therapy*
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Malaria, Falciparum / metabolism
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Pregnancy
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Pregnancy Complications, Parasitic / blood
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Pregnancy Complications, Parasitic / drug therapy*
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Pregnancy Complications, Parasitic / metabolism
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Pregnancy Outcome
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Pregnancy Trimester, Second
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Pregnancy Trimester, Third
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Proguanil / administration & dosage
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Proguanil / pharmacokinetics
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Proguanil / therapeutic use
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Sesquiterpenes / administration & dosage
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Sesquiterpenes / pharmacokinetics*
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Sesquiterpenes / therapeutic use
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Thailand
Substances
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Antimalarials
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Artemisinins
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Drug Combinations
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Sesquiterpenes
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Artesunate
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artenimol
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Proguanil
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Atovaquone