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The impact of genetic variability on Alzheimer's therapies: obstacles for pharmacogenetic progress.
Expert Opin Drug Metab Toxicol
January 2025
EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, Bergondo, Corunna, Spain.
Introduction: Genetic load influences the therapeutic response to conventional drugs in Alzheimer's disease (AD). Pharmacogenetics (PGx) is the best option to reduce drug-drug interactions and adverse drug reactions in patients undergoing polypharmacy regimens. However, there are important limitations that make it difficult to incorporate pharmacogenetics into routine clinical practice.
View Article and Find Full Text PDFPharmacogenetic associations of GATA4 and KCNQ1 with ibrutinib cardiovascular toxicity.
Pharmacogenet Genomics
January 2025
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g.
View Article and Find Full Text PDFValidating the accuracy of mathematical model-based pharmacogenomics dose prediction with real-world data.
Eur J Clin Pharmacol
January 2025
Electrical and Computer Engineering Department, School of Engineering, Lebanese American University, P.O. Box: 36, Byblos, F-19, Lebanon.
Objective: The study aims to verify the usage of mathematical modeling in predicting patients' medication doses in association with their genotypes versus real-world data.
Methods: The work relied on collecting, extracting, and using real-world data on dosing and patients' genotypes. Drug metabolizing enzymes, i.
Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses.
Sci Rep
January 2025
Institute for Breath Research, University of Innsbruck, Innrain 80/82, Innsbruck, 6020, Austria.
Cytochrome P450 (CYP) 3A4 plays a major role in drug metabolism. Its activity could be determined by non-invasive and cost-effective assays, such as breath analysis, for the personalised monitoring of drug response. For the first time, we identify an isotopically unlabelled CYP3A4 substrate, tolterodine that leads to the formation of a non-toxic volatile metabolite, acetone, which could potentially be applied to monitor CYP3A4 activity in humans.
View Article and Find Full Text PDFHeterotypic spheroids as a strategy for 3D culture of cryopreserved primary human hepatocytes in stirred-tank systems.
SLAS Discov
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12 2781-901 Oeiras, Portugal; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Av. Republica, 2780-157, Oeiras, Portugal. Electronic address:
Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability.
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