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Atorvastatin-associated myotoxicity: A toxicokinetic review of pharmacogenetic associations to evaluate the feasibility of precision pharmacotherapy.
Clin Biochem
February 2024
Integrated PharmacoMetrics, pharmacoGenomics and Pharmacokinetics, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), Brussels 1200, Belgium; Louvain Center for Toxicology and Applied Pharmacology, Institut de recherche expérimentale et clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium. Electronic address:
Atorvastatin (ATV) and other statins are highly effective in reducing cholesterol levels. However, in some patients, the development of drug-associated muscle side effects remains an issue as it compromises the adherence to treatment. Since the toxicity is dose-dependent, exploring factors modulating pharmacokinetics (PK) appears fundamental.
View Article and Find Full Text PDFA gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance.
Eur Heart J Cardiovasc Pharmacother
September 2023
Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Population Health & Genomics, School of Medicine, Ninewells Hospital & Medical School, University of Dundee, DundeeDD1 9SY, UK.
Background And Aims: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentrations of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping.
View Article and Find Full Text PDFProgression of precision statin prescribing for reduction of statin-associated muscle symptoms.
Pharmacogenomics
July 2022
Department of Population Medicine, PRecisiOn Medicine Translational Research (PROMoTeR) Center, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA.
Statins are among the most commonly prescribed medications, and improve patient outcomes by lowering cholesterol levels, but also have side effects. Variations in statin response can be attributed to a handful of factors that include pharmacogenetics. While not a true review article, this work was written using various search engines and terms and previous and newly published Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statins to provide a historical perspective in addition to the current status of statin-related pharmacogenetics and future perspectives.
View Article and Find Full Text PDFGenetic Variant rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia.
Pharmaceutics
April 2022
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods.
View Article and Find Full Text PDFPharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts.
Pharmacol Rep
February 2022
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580, Sao Paulo, 05508-000, Brazil.
Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in cholesterol biosynthesis, that are highly effective in reducing plasma low-density lipoprotein (LDL) cholesterol and decreasing the risk of cardiovascular events. In recent years, a multitude of variants in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) have been suggested to influence the cholesterol-lowering response. However, the vast majority of studies have analyzed the pharmacogenetic associations in populations in Europe and the USA, whereas data in other populations, including Brazil, are mostly lacking.
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