ArticleAntimicrobial agents and chemotherapy2015
Differential cytochrome P450 2D metabolism alters tafenoquine pharmacokinetics.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial.The Lancet. Microbe · 2022Trial
- 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
- CYP3A and CYP2D6 variability in antimalarial pharmacokinetics and pharmacogenetics across populations: a narrative review.Malaria journal · 2026Review
- Differential impact of Tafenoquine and Primaquine onAntimicrobial agents and chemotherapy · 2026Article
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Enhancing CYP2D6 genotyping with nanopore sequencing to address allele diversity P. vivax malaria elimination.Scientific reports · 2025Article
- Evaluation of in vitro drug-drug interactions of ivermectin and antimalarial compounds.Malaria journal · 2025Article
- Fractional curative killing of pyronaridine or artesunate combinations with tafenoquine, 4-aminoquinolines, or azithromycin in a murine malaria-luciferase model.Antimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetic Models of Tafenoquine: Insights for Optimal Malaria Treatment Strategies.Pharmaceutics · 2024Review
- Safety, pharmacokinetics, and potential neurological interactions of ivermectin, tafenoquine, and chloroquine in Rhesus macaques.Antimicrobial agents and chemotherapy · 2024Article
- Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure.Science advances · 2024Article
- Article
- Cytochrome P450 2D6 profiles and anti-relapse efficacy of tafenoquine againstAntimicrobial agents and chemotherapy · 2023Article
- Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study.Molecules (Basel, Switzerland) · 2022Article
- Article
- Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.International journal for parasitology. Drugs and drug resistance · 2021Review
- Article
- Tafenoquine: A Step toward Malaria Elimination.Biochemistry · 2020Article
- Determination of Cytochrome P450 Isoenzyme 2D6 (CYP2D6) Genotypes and Pharmacogenomic Impact on Primaquine Metabolism in an Active-Duty US Military Population.The Journal of infectious diseases · 2019Article
- Protozoan persister-like cells and drug treatment failure.Nature reviews. Microbiology · 2019Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial efficacy of the 8-aminoquinoline molecule tafenoquine in mice. This could be problematic for Plasmodium vivax radical cure, as the human CYP 2D ortholog (2D6) is highly polymorphic. Diminished CYP 2D6 enzyme activity, as in the poor-metabolizer phenotype, could compromise radical curative efficacy in humans. Despite the importance of CYP 2D metabolism for tafenoquine liver-stage efficacy, the exact role that CYP 2D metabolism plays in the metabolism and pharmacokinetics of tafenoquine and other 8-aminoquinoline molecules has not been extensively studied. In this study, a series of tafenoquine pharmacokinetic experiments were conducted in mice with different CYP 2D metabolism statuses, including wild-type (WT) (reflecting extensive metabolizers for CYP 2D6 substrates) and CYPmouse 2D knockout (KO) (reflecting poor metabolizers for CYP 2D6 substrates) mice. Plasma and liver pharmacokinetic profiles from a single 20-mg/kg of body weight dose of tafenoquine differed between the strains; however, the differences were less striking than previous results obtained for primaquine in the same model. Additionally, the presence of a 5,6-ortho-quinone tafenoquine metabolite was examined in both mouse strains. The 5,6-ortho-quinone species of tafenoquine was observed, and concentrations of the metabolite were highest in the WT extensive-metabolizer phenotype. Altogether, this study indicates that CYP 2D metabolism in mice affects tafenoquine pharmacokinetics and could have implications for human tafenoquine pharmacokinetics in polymorphic CYP 2D6 human populations.
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