Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies have shown that the kinetics of artemisinins derivatives, most specifically of the active metabolite dihydroartemisinin, is modified during pregnancy.
“Several studies have shown that the kinetics of artemisinins derivatives, most specifically of the active metabolite dihydroartemisinin, is modified during pregnancy.133–134”
From Malaria in pregnancy. (2013) · cites this paper as [134]
Cites
McGready, R., Cho, T., Keo, N. K., Thwai, K. L., Villegas, L., Looareesuwan, S., White, N. J., & Nosten, F. (2001) · Clinical Infectious Diseases · doi:10.1086/324349 · Cited by 178 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Antiviral Activities of Artemisinin and Artesunate
Efferth, T., Romero, M. R., Wolf, D. G., Stamminger, T., Marin, J. J. G., & Marschall, M. (2008) · Clinical Infectious Diseases · doi:10.1086/591195 · Cited by 503 · see citing works
Malaria in pregnancy in the Asia-Pacific region
Rijken, M. J., McGready, R., Boel, M. E., Poespoprodjo, R., Singh, N., Syafruddin, D., Rogerson, S., & Nosten, F. (2012) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(11)70315-2 · Cited by 181 · see citing works
Self-citationTakem, E. N., & D'Alessandro, U. (2013) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2013.010 · Cited by 185 · see citing works
McGready, R., Tan, S. O., Ashley, E. A., Pimanpanarak, M., Viladpai-nguen, J., Phaiphun, L., Wüstefeld, K., Barends, M., Laochan, N., Keereecharoen, L., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050253 · Cited by 136 · see citing works
Self-citationMayor, A., Serra-Casas, E., Bardají, A., Sanz, S., Puyol, L., Cisteró, P., Sigauque, B., Mandomando, I., Aponte, J. J., Alonso, P. L., et al. (2009) · Malaria Journal · doi:10.1186/1475-2875-8-9 · Cited by 105 · see citing works
Tarning, J., Rijken, M. J., McGready, R., Phyo, A. P., Hanpithakpong, W., Day, N. P. J., White, N. J., Nosten, F., & Lindegardh, N. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05756-11 · Cited by 102 · see citing works
Self-citationTreating Severe Malaria in Pregnancy: A Review of the Evidence
Kovacs, S. D., Rijken, M. J., & Stergachis, A. (2015) · Drug Safety · doi:10.1007/s40264-014-0261-9 · Cited by 66 · see citing works
Cohort Profile: the SMRU Refugee and Migrant Pregnancy Study in Western Thailand and Eastern Myanmar
McGready, R., J White, N., Nosten, F. H., & Collaborators, S. R. A. M. P. S. (2026) · Wellcome Open Research · doi:10.12688/wellcomeopenres.25582.2 · Cited by 2 · see citing works
Self-citation
- Authors
- McGready, R., Stepniewska, K., Ward, S. A., Cho, T., Gilveray, G., Looareesuwan, S., White, N. J., & Nosten, F.
- Affiliations
- Mahidol University (TH)
- Liverpool School of Tropical Medicine (GB)
- Shoklo Malaria Research Unit (TH)
- Corresponding author
- White, N. J.
- Venue
- European Journal of Clinical Pharmacology
- Published
- 2006-03-22
- Volume
- 62
- Issue
- 5
- Pages
- 367-371
- ISSN
- 0031-6970 (ISSN-L)
- 1432-1041
- OpenAlex
- W2046220151
- Cited by
- 101
- References
- 1
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 9
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- dihydroartemisinin, artesunate, pharmacokinetics, pregnancy, falciparum malaria, Plasmodium falciparum, atovaquone-proguanil, multidrug resistance, recrudescent malaria, dose optimization, pregnancy trimesters
- MeSH terms
- Artesunate, Acute Disease, Adolescent, Adult, Analysis of Variance, Antimalarials, Proguanil, Drug Combinations, Drug Therapy, Combination, Female, Half-Life, Humans, Pregnancy, Pregnancy Outcome, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Sesquiterpenes, Thailand, Pregnancy Complications, Parasitic, Malaria, Falciparum, Drug Resistance, Multiple, Artemisinins, Atovaquone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
