ArticleMalaria journal2013
The metabolism of primaquine to its active metabolite is dependent on CYP 2D6.
Article in Malaria journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 113 papers.
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.
Development of Safer Drugs for Malaria in U.S. Troops, Civilian Personnel, and Travelers: Clinical Evaluation of Primaquine Enantiomer
A Clinical Study to Assess the Safety and Feasibility of Controlled Blood-stage Plasmodium Vivax Human Malaria Infection Through Experimental Inoculation of Cryopreserved Infected Erythrocytes in Healthy Thai Adults
Who cites it
113 citing papers in PubMed, 183 citations in OpenAlex.
- A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania.Malaria journal · 2022Trial
- Determinants of Primaquine and Carboxyprimaquine Exposures in Children and Adults with Plasmodium vivax Malaria.Antimicrobial agents and chemotherapy · 2021Trial
- Trial
- Pharmacokinetics/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine.Malaria journal · 2019Trial
- Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial.Malaria journal · 2019Trial
- Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.The New England journal of medicine · 2019Trial
- Enantiospecific pharmacokinetics and drug-drug interactions of primaquine and blood-stage antimalarial drugs.The Journal of antimicrobial chemotherapy · 2018Trial
- Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Trial
- Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Piperaquine Monotherapy of Drug-Susceptible Plasmodium falciparum Infection Results in Rapid Clearance of Parasitemia but Is Followed by the Appearance of Gametocytemia.The Journal of infectious diseases · 2016Trial
- Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial.Malaria journal · 2016Trial
- Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia.BMC medicine · 2015Trial
- Pharmacokinetic interactions between primaquine and pyronaridine-artesunate in healthy adult Thai subjects.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetic interactions between primaquine and chloroquine.Antimicrobial agents and chemotherapy · 2014Trial
- Primaquine-derived 5,6-orthoquinone concentrations in urine associated with CYP2D6 genotype-predicted phenotype and blood methemoglobin levels.Antimicrobial agents and chemotherapy · 2026Article
- An orally available PfPKG inhibitor blocks Plasmodium's infection of the liver.PLoS pathogens · 2026Article
- Differential impact of Tafenoquine and Primaquine onAntimicrobial agents and chemotherapy · 2026Article
- Humanization of Drug Metabolism in theACS infectious diseases · 2025Article
- How CYP2D6 Polymorphism Modulates the Community-Wide Risk of Plasmodium vivax Infection: A Panel Study in Amazonian Brazil.The Journal of infectious diseases · 2025Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites.
methodsIn the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity.
resultsPQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice.
conclusionsThese results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.
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What OpenQuestion holds
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.