Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases

León, Mario Bermúdez de; León-Cachón, Rafael B. R.; Silva-Ramírez, Beatriz; González-Ríos, Rosa Nelly; Escobedo-Guajardo, Brenda Leticia; Leyva-Parra, Roberto; Tovar-Cisneros, Benjamín; Gonzalez‐González, Everardo; Alvarado-Díaz, Abdiel; Vázquez-Monsiváis, Ofelia; Mata-Tijerina, Viviana; Puente-Lugo, Lorena; Álvarez-Galván, Erick; Currás-Tuala, María José; Aguado-Barrera, Miguel E.; Castorena‐Torres, Fabiola; Alcocer‐González, Juan Manuel; Elizondo, Guillermo; Salinas-Martı́nez, Ana Marı́a

doi:10.1038/s41397-020-0151-8

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…The SNP rs71647871 of CES1 has been found to be associated with variation in plasma concentration-time curve of oseltamivir (Tarkiainen et al, 2012) The PK of oseltamivir may also be affected by the ABCB1, CES1, NEU2, and SLC15A1 genetic variants. The SNP rs1045642 of ABCB1 was associated with neurologic ADRs developed by oseltamivir (Bermúdez de León et al, 2020;Fricke-Galindo and Falfán-Valencia, 2021).…”

Section: Oseltamivirmentioning

confidence: 99%

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

et al. 2022

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Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug–gene pairs (atazanavir–UGT1A1, ABCB1, SLCO1B1, APOA5; efavirenz–CYP2B6; nevirapine–HLA, CYP2B6, ABCB1; lopinavir–SLCO1B3, ABCC2; ribavirin–SLC28A2; tocilizumab–FCGR3A; ivermectin–ABCB1; oseltamivir–CES1, ABCB1; clopidogrel–CYP2C19, ABCB1, warfarin–CYP2C9, VKORC1; non-steroidal anti-inflammatory drugs (NSAIDs)–CYP2C9) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from in silico studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug–drug interactions (DDIs) and drug–herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and CYP2B6) and herbogenetic (e.g., andrographolide and CYP2C9) interventions, collectively called multifactorial drug–gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.

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Section: Oseltamivirmentioning

confidence: 99%

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

et al. 2022

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“…Another study evaluated the association of oseltamivir ADRs with variants in ABCB1 , CES1 , NEU2 , and SLC15A1 , the gene encoding the transporter PepT1. Authors found that ABCB1 rs1045642 was related to ADRs under the recessive model; the C allele was more frequently found among patients who did not present ADRs, while the T allele was predominant in the group of individuals who did report ADRs [ 52 ].…”

Section: Current Drugs Employed In the Covid-19 Treatmentmentioning

confidence: 99%

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Fricke-Galindo

Falfán-Valencia

2021

Viruses

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The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug–drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19.

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“…Additionally, we report that this subpar protection promotes the emergence of influenza viral variants with increased neuraminidase (NA) activity and greater oseltamivir resistance. Together, these findings suggest study is warranted on how host characteristics can influence pharmaceutical efficacy ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of oseltamivir treatment in influenza virus-infected obese mice

Honce

Jones

Meliopoulos

et al. 2023

mBio

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Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, is suggested to begin within days of infection especially in high-risk hosts. However, this treatment can be poorly effective and may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectiveness in the genetically obese mouse model. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistance in vitro . Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population. IMPORTANCE Influenza virus infections, while typically resolving within days to weeks, can turn critical, especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I interferon receptor-deficient mice. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants.

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Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases

Cited by 3 publications

References 40 publications

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Efficacy of oseltamivir treatment in influenza virus-infected obese mice

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