Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Anticonvulsivantes/farmacología , Anticonvulsivantes/farmacocinética , Encéfalo/metabolismo , Lamotrigina/farmacología , Lamotrigina/farmacocinética , Proteínas de Transporte de Monosacáridos/genética , Receptores de GABA/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Anticonvulsivantes/efectos adversos , Canales de Calcio Tipo Q/genética , Canales de Calcio Tipo Q/metabolismo , Humanos , Lamotrigina/efectos adversos , Proteínas de Transporte de Monosacáridos/metabolismo , Polimorfismo Genético , Receptores de GABA/metabolismoAsunto(s)
Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Farmacogenética , Voriconazol/uso terapéutico , Antifúngicos/farmacocinética , Aspergillus/efectos de los fármacos , Aspergillus/patogenicidad , Candida/efectos de los fármacos , Candida/patogenicidad , Fusarium/efectos de los fármacos , Fusarium/patogenicidad , Humanos , Micosis/genética , Micosis/microbiología , Scedosporium/efectos de los fármacos , Scedosporium/patogenicidad , Voriconazol/farmacocinéticaAsunto(s)
ADN Mitocondrial/genética , Pérdida Auditiva/genética , Farmacogenética , ARN Ribosómico/genética , Ribonucleótido Reductasas/genética , Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Predisposición Genética a la Enfermedad , Variación Genética , Pérdida Auditiva/tratamiento farmacológico , Pérdida Auditiva/patología , Humanos , MutaciónRESUMEN
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
Asunto(s)
Citocromo P-450 CYP2C19/genética , Farmacogenética/métodos , Inhibidores de la Bomba de Protones/administración & dosificación , Reflujo Gastroesofágico/tratamiento farmacológico , Genotipo , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/farmacocinéticaRESUMEN
Precision medicine tailors treatment to individuals personal data including differences in their genome. The Pharmacogenomics Knowledgebase (PharmGKB) provides highly curated information on the effect of genetic variation on drug response and side effects for a wide range of drugs. PharmGKB's scientific curators triage, review and annotate a large number of papers each year but the task is challenging. We present the PGxMine resource, a text-mined resource of pharmacogenomic associations from all accessible published literature to assist in the curation of PharmGKB. We developed a supervised machine learning pipeline to extract associations between a variant (DNA and protein changes, star alleles and dbSNP identifiers) and a chemical. PGxMine covers 452 chemicals and 2,426 variants and contains 19,930 mentions of pharmacogenomic associations across 7,170 papers. An evaluation by PharmGKB curators found that 57 of the top 100 associations not found in PharmGKB led to 83 curatable papers and a further 24 associations would likely lead to curatable papers through citations. The results can be viewed at https://pgxmine.pharmgkb.org/ and code can be downloaded at https://github.com/jakelever/pgxmine.
Asunto(s)
Farmacogenética , Medicina de Precisión , Biología Computacional , Minería de Datos/métodos , Bases de Datos Genéticas , Humanos , Bases del Conocimiento , Medicina de Precisión/métodosAsunto(s)
Ciclosporina , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Inmunosupresores , Tacrolimus , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Calcineurina/genética , Calcineurina/metabolismo , Ciclosporina/farmacocinética , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Citocromo P-450 CYP3A/genética , Variación Genética , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Sistema de Señalización de MAP Quinasas , Trasplante de Órganos , Farmacogenética , Polimorfismo Genético , Tacrolimus/farmacocinética , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
As precision medicine becomes increasingly relevant in healthcare, the field of pharmacogenomics (PGx) also continues to gain prominence in the clinical setting. Leading institutions have begun to implement PGx testing and the amount of published PGx literature increases yearly. The Pharmacogenomics Knowledgebase (PharmGKB; www.pharmgkb.org) is one of the foremost worldwide resources for PGx knowledge, and the organization has been adapting and refocusing its mission along with the current revolution in genomic medicine. The PharmGKB website provides a diverse array of PGx information, from annotations of the primary literature to guidelines for adjusting drug treatment based on genetic information. It is freely available and accessible to everyone from researchers to clinicians to everyday citizens. PharmGKB was found over 17 years ago, but continues to be a vital resource for the entire PGx community and the general public. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine.
Asunto(s)
Farmacogenética , Medicina de Precisión , Bases de Datos Factuales , Células Germinativas/metabolismo , Guías como Asunto , Antígenos HLA-B/genética , Antígenos HLA-B/metabolismo , Humanos , FarmacocinéticaRESUMEN
The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5-fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost-effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC® ) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/).