Trial reportMalaria journal2011
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria.
Trial report in Malaria journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review.Malaria journal · 2016Pooled it
- Pooled it
- A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy.Malaria journal · 2012Pooled it
- Opposite malaria and pregnancy effect on oral bioavailability of artesunate - a population pharmacokinetic evaluation.British journal of clinical pharmacology · 2015Trial
- Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer.European journal of clinical pharmacology · 2014Trial
- Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso.The Journal of antimicrobial chemotherapy · 2014Trial
- Dihydroartemisinin attenuates lipopolysaccharide‑induced acute lung injury in mice by suppressing NF‑κB signaling in an Nrf2‑dependent manner.International journal of molecular medicine · 2019Article
- Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicatedWellcome open research · 2019Article
- Treatment of uncomplicated and severe malaria during pregnancy.The Lancet. Infectious diseases · 2018Review
- Population Pharmacokinetic and Pharmacodynamic Modeling of Artemisinin Resistance in Southeast Asia.The AAPS journal · 2017Article
- Population pharmacokinetics, tolerability, and safety of dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine-piperaquine in pregnant and nonpregnant Papua New Guinean women.Antimicrobial agents and chemotherapy · 2015Article
- Treating severe malaria in pregnancy: a review of the evidence.Drug safety · 2015Review
- Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges.British journal of clinical pharmacology · 2015Review
- Obstetric Pharmacokinetic Dosing Studies are Urgently Needed.Frontiers in pediatrics · 2014Review
- Pharmacokinetics of piperaquine in pregnant women in Sudan with uncomplicated Plasmodium falciparum malaria.The American journal of tropical medicine and hygiene · 2012Article
- Know your enemy: understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics.Cellular and molecular life sciences : CMLS · 2012Review
- Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects.British journal of clinical pharmacology · 2012Article
- Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria.Antimicrobial agents and chemotherapy · 2011Article
- Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration.Malaria journal · 2011Review
- Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria.Malaria journal · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC.
methodsData were obtained from 26 pregnant women in the second (22-26 weeks) or the third (32-36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling.
resultsA simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7-72.3%).
conclusionsIn this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.