Pharmacokinetics of Dihydroartemisinin and Piperaquine in Pregnant and Nonpregnant Women with Uncomplicated Falciparum Malaria
Open accessAbstract
Dihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days. Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma dihydroartemisinin and piperaquine concentrations were analyzed by liquid chromatography-mass spectrometry. Piperaquine and dihydroartemisinin pharmacokinetics were well described. There were no significant differences in total piperaquine exposure ( P = 0.80) or drug exposure during the terminal elimination phase (72 h to infinity) ( P = 0.64) between the two groups. The apparent volume of distribution of piperaquine was significantly smaller (602 liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women ( P = 0.0057), and the terminal elimination half-life was significantly shorter (17.8 days versus 25.6 days; P = 0.0023). Dihydroartemisinin exposure after the first dose was significantly lower (844 h × ng/ml versus 1,220 h × ng/ml, P = 0.0021) in pregnant women, but there were no significant differences in total dihydroartemisinin exposure or maximum concentrations between the two groups. There were no significant differences in any pharmacokinetic parameters between the second and third trimester. These results obtained through noncompartmental analysis suggest that in the treatment of falciparum malaria, there are no clinically important differences in the pharmacokinetics of dihydroartemisinin or piperaquine between pregnant and nonpregnant women. However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life.
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Dihydroartemisinin piperaquine (DHAPQ) was highly effective in women with multiple recrudescent infections on the Thai-Burmese border.
“Dihydroartemisinin piperaquine (DHAPQ) was highly effective in women with multiple recrudescent infections on the Thai-Burmese border.140”
From Malaria in pregnancy. (2013) · cites this paper as [140]
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- Authors
- Rijken, M. J., McGready, R., Phyo, A. P., Lindegardh, N., Tarning, J., Laochan, N., Than, H. H., Mu, O., Win, A. K., Singhasivanon, P., White, N., & Nosten, F.
- Affiliations
- Shoklo Malaria Research Unit (TH)
- Mahidol University (TH)
- Shoklo Malaria Research Unit, P.O. Box 46 Mae Sot, Tak 63110, Thailand
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Corresponding author
- Nosten, François
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2011-12
- Volume
- 55
- Issue
- 12
- Pages
- 5500-5506
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3232755
- OpenAlex
- W2155629163
- Cited by
- 75
- References
- 5
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 9 · 2016: 9 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 8
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bill and Melinda Gates Foundation
- Wellcome Trust
- University of Oxford
- Mahidol University
- 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 › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- dihydroartemisinin, piperaquine, dihydroartemisinin-piperaquine, falciparum malaria, pregnancy, pharmacokinetics, volume of distribution, elimination half-life, drug exposure, pregnancy trimesters, artemisinin-based combination therapy
- MeSH terms
- Adult, Antimalarials, Drug Administration Schedule, Drug Therapy, Combination, Female, Half-Life, Humans, Piperazines, Pregnancy, Pregnancy Outcome, Quinolines, Thailand, Pregnancy Complications, Parasitic, Malaria, Falciparum, Area Under Curve, Artemisinins, Young Adult
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