Trial reportAntimicrobial agents and chemotherapy2008
Effect of concomitant artesunate administration and cytochrome P4502C8 polymorphisms on the pharmacokinetics of amodiaquine in Ghanaian children with uncomplicated malaria.
Trial report in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Pooled it
- Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.Antimicrobial agents and chemotherapy · 2018Trial
- Trial
- Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African-American volunteers.Pharmacotherapy · 2013Trial
- Population pharmacokinetics and pharmacodynamic considerations of amodiaquine and desethylamodiaquine in Kenyan adults with uncomplicated malaria receiving artesunate-amodiaquine combination therapy.Antimicrobial agents and chemotherapy · 2010Trial
- Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: Clinical and preclinical studies.British journal of clinical pharmacology · 2023Article
- The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review.Pharmacogenomics and personalized medicine · 2023Review
- Pharmacogene Sequencing of a Gabonese Population with Severe Plasmodium falciparum Malaria Reveals Multiple Novel Variants with Putative Relevance for Antimalarial Treatment.Antimicrobial agents and chemotherapy · 2021Article
- Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar.Malaria journal · 2021Article
- Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria.Malaria journal · 2021Article
- Influence ofAntimicrobial agents and chemotherapy · 2020Article
- Adherence and Population Pharmacokinetic Properties of Amodiaquine When Used for Seasonal Malaria Chemoprevention in African Children.Clinical pharmacology and therapeutics · 2020Article
- Prevalence ofPharmacogenomics and personalized medicine · 2020Article
- Population Pharmacokinetic Estimates Suggest Elevated Clearance and Distribution Volume of Desethylamodiaquine in Pediatric Patients with Sickle Cell Disease Treated with Artesunate-Amodiaquine.Current therapeutic research, clinical and experimental · 2019Article
- Pharmacokinetics and Safety Profile of Artesunate-Amodiaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.Antimicrobial agents and chemotherapy · 2018Article
- Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria.Antimicrobial agents and chemotherapy · 2018Article
- A Review of Pharmacogenetics of Antimalarials and Associated Clinical Implications.European journal of drug metabolism and pharmacokinetics · 2017Review
- Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations.Malaria journal · 2014Article
- Pharmacogenomics of antimicrobial agents.Pharmacogenomics · 2014Review
- Frequencies of Cytochrome P450 2B6 and 2C8 Allelic Variants in the Mozambican Population.The Malaysian journal of medical sciences : MJMS · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Artesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma between patients with different variants of the cytochrome P4502C8 (CYP2C8) gene. A two-compartment model was fitted to 169 plasma DEAQ concentrations from 103 Ghanaian children aged 1 to 14 years with uncomplicated malaria treated either with AQ alone (n = 15) or with AS plus AQ (n = 88). The population clearance of DEAQ appeared to increase nonlinearly with body weight, and the central volume of distribution of DEAQ was higher (P < 0.001) in the AS-plus-AQ group than in the AQ-only group. The maximum plasma DEAQ concentration was higher (P < 0.001), and the population distribution half-life was shorter (P < 0.01), in the AQ-only group than in the AS-plus-AQ group. The total areas under the plasma DEAQ concentration-time curves (P = 0.68) and elimination half-lives (P = 0.39) were similar for the two groups. There was a high frequency (0.179) of the non-wild-type allele of CYP2C8, but no differences between CYP2C8 genotypes with regard to AQ efficacy or safety were evident. The sample size, however, was limited, so monitoring of AQ toxicity in the study area is still indicated. The nonlinear clearance of DEAQ and the wide variability in kinetic parameters have safety implications for weight-based dosing of higher-body-weight children with AQ. The pharmacokinetics of artemisinin combination therapies should be studied in malaria patients, because the rapid parasite clearance caused by the artemisinin may affect the kinetics of the partner drug and the combination.
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