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

McGready, R., Stepniewska, K., Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192, Cho, T., Gilveray, G., Looareesuwan, S., White, N. J. and Nosten, F. (2005) 'Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria'. European Journal of Clinical Pharmacology, Vol 62, Issue 5, pp. 367-371.

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Abstract

Objective: 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(-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] 1 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.

Item Type:	Article
Uncontrolled Keywords:	malaria plasmodium falciparum artesunate dha pharmacokinetics pregnancy plasmodium-falciparum mefloquine combination atovaquone resistance proguanil plasma drug
Subjects:	QV Pharmacology > QV 38 Drug action. QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WQ Obstetrics > Pregnancy > WQ 200 General works WQ Obstetrics > Pregnancy Complications > WQ 240 Pregnancy complications (General) WQ Obstetrics > Pregnancy Complications > WQ 256 Infectious diseases
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1007/s00228-006-0118-y
Depositing User:	Sarah Lewis-Newton
Date Deposited:	18 Oct 2011 10:27
Last Modified:	06 Feb 2018 13:02
URI:	https://archive.lstmed.ac.uk/id/eprint/1887

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