ArticleThe Journal of infectious diseases2019
Determination of Cytochrome P450 Isoenzyme 2D6 (CYP2D6) Genotypes and Pharmacogenomic Impact on Primaquine Metabolism in an Active-Duty US Military Population.
Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 18 papers.
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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.
Genetic Variability in the Cytochrome P-450 Isoenzyme 2D6 (CYP2D6) in an Active Duty U.S. Military Population and the Impact of CYP2D6 Phenotype on Primaquine Metabolism.
Safety, Tolerability and Pharmacokinetics of Tafenoquine After Weekly and Escalating Monthly Doses of Tafenoquine in Healthy Vietnamese Volunteers
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Primaquine-derived 5,6-orthoquinone concentrations in urine associated with CYP2D6 genotype-predicted phenotype and blood methemoglobin levels.Antimicrobial agents and chemotherapy · 2026Article
- Review
- Primaquine-5,6-Orthoquinone Is Directly Hemolytic to Older G6PD Deficient RBCs in a Humanized Mouse Model.The Journal of pharmacology and experimental therapeutics · 2024Article
- Delayed gametocyte clearance inAntimicrobial agents and chemotherapy · 2024Article
- Article
- Plasmodium vivax: the potential obstacles it presents to malaria elimination and eradication.Tropical diseases, travel medicine and vaccines · 2022Review
- Article
- Measurements of 5,6-Orthoquinone, a Surrogate for the Presumed Active Primaquine Metabolite 5-Hydroxyprimaquine, in the Urine of Cambodian Adults.Antimicrobial agents and chemotherapy · 2022Article
- Comparative pharmacokinetics and tissue distribution of primaquine enantiomers in mice.Malaria journal · 2022Article
- Comparative metabolism and tolerability of racemic primaquine and its enantiomers in human volunteers during 7-day administration.Frontiers in pharmacology · 2022Article
- Simplified and Rapid Determination of Primaquine and 5,6-Orthoquinone Primaquine by UHPLC-MS/MS: Its Application to a Pharmacokinetic Study.Molecules (Basel, Switzerland) · 2021Article
- Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.International journal for parasitology. Drugs and drug resistance · 2021Review
- Synthesis, Biological Activity and In Silico Pharmacokinetic Prediction of a New 2-Thioxo-Imidazoldidin-4-One of Primaquine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites.Scientific reports · 2021Article
- Article
- Prevalence of CYP2D6 Genotypes and Predicted Phenotypes in a Cohort of Cambodians at High Risk for Infections withThe American journal of tropical medicine and hygiene · 2020Article
- Tafenoquine: A Step toward Malaria Elimination.Biochemistry · 2020Article
- Pharmacogene Variation in ThaiPharmacogenomics and personalized medicine · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPlasmodium vivax malaria requires a 2-week course of primaquine (PQ) for radical cure. Evidence suggests that the hepatic isoenzyme cytochrome P450 2D6 (CYP2D6) is the key enzyme required to convert PQ into its active metabolite.
methodsCYP2D6 genotypes and phenotypes of 550 service personnel were determined, and the pharmacokinetics (PK) of a 30-mg oral dose of PQ was measured in 45 volunteers. Blood and urine samples were collected, with PQ and metabolites were measured using ultraperformance liquid chromatography with mass spectrometry.
resultsSeventy-six CYP2D6 genotypes were characterized for 530 service personnel. Of the 515 personnel for whom a single phenotype was predicted, 58% had a normal metabolizer (NM) phenotype, 35% had an intermediate metabolizer (IM) phenotype, 5% had a poor metabolizer (PM) phenotype, and 2% had an ultrametabolizer phenotype. The median PQ area under the concentration time curve from 0 to ∞ was lower for the NM phenotype as compared to the IM or PM phenotypes. The novel 5,6-ortho-quinone was detected in urine but not plasma from all personnel with the NM phenotype.
conclusionThe plasma PK profile suggests PQ metabolism is decreased in personnel with the IM or PM phenotypes as compared to those with the NM phenotype. The finding of 5,6-ortho-quinone, the stable surrogate for the unstable 5-hydroxyprimaquine metabolite, almost exclusively in personnel with the NM phenotype, compared with sporadic or no production in those with the IM or PM phenotypes, provides further evidence for the role of CYP2D6 in radical cure. CLINICAL TRIALS REGISTRATION: NCT02960568.
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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.