Trial reportAntimicrobial agents and chemotherapy2018
Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.
Trial report in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.PLoS medicine · 2021Pooled it
- Population pharmacokinetics of artemether-lumefantrine plus amodiaquine in patients with uncomplicated Plasmodium falciparum malaria.British journal of clinical pharmacology · 2026Trial
- Model-Informed Drug Development of Subcutaneous Nivolumab: Comparison of Pharmacokinetic Analysis Methodologies Using Clinical Trial Simulation.CPT: pharmacometrics & systems pharmacology · 2025Trial
- Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Unanticipated CNS Safety Signal in a Placebo-Controlled, Randomized Trial of Co-Administered Atovaquone-Proguanil and Amodiaquine.Clinical pharmacology and therapeutics · 2022Trial
- Development of a Disease-Specific Virtual Malaria Population for Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2026Article
- Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis.The Journal of antimicrobial chemotherapy · 2026Article
- Cohort Profile: the SMRU Refugee and Migrant Pregnancy Study in Western Thailand and Eastern Myanmar.Wellcome open research · 2026Article
- Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms.Archives of microbiology · 2025Review
- Use of population pharmacokinetic-pharmacodynamic modelling to inform antimalarial dose optimization in infants.British journal of clinical pharmacology · 2025Review
- A LC-MS/MS Assay for Quantification of Amodiaquine and Desethylamodiaquine in Dried Blood Spots on Filter Paper.International journal of analytical chemistry · 2025Article
- Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: Clinical and preclinical studies.British journal of clinical pharmacology · 2023Article
- The assessment of antimalarial drug efficacy in vivo.Trends in parasitology · 2022Review
- Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization.Antimicrobial agents and chemotherapy · 2022Article
- Development of single- and multiplex immunoassays for rapid detection and quantitation of amodiaquine in ACT drugs and rat serum.Analytical and bioanalytical chemistry · 2022Article
- Population Pharmacokinetics of Diethylcarbamazine in Patients with Lymphatic Filariasis and Healthy Individuals.Antimicrobial agents and chemotherapy · 2021Article
- Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria.Malaria journal · 2021Article
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Investigating selected host and parasite factors potentially impacting upon seasonal malaria chemoprevention in Bama, Burkina Faso.Malaria journal · 2020Article
- Adherence and Population Pharmacokinetic Properties of Amodiaquine When Used for Seasonal Malaria Chemoprevention in African Children.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 12 institutions in 11 countries.
Funding
Abstract
Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.
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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.