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Association of NR1I2 Polymorphism with Midazolam Clearance in Mechanically Ventilated ICU Patients: A Population Pharmacokinetic and Pharmacogenetic Study.
Drug Des Devel Ther
March 2025
Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, People's Republic of China.
Background: Significant variability in the metabolism of midazolam (MDZ) exists among mechanically ventilated (MV) patients in the intensive care unit (ICU) due to complex clinical conditions and genetic factors. The NR1I2 gene (PXR), which encodes a nuclear receptor that regulates drug-metabolizing enzymes like CYP3A4, plays a critical role in MDZ metabolism. Polymorphisms in NR1I2, along with variations in genes such as CYP3A4, CYP3A5, and ABCB1, may influence enzyme activity and MDZ pharmacokinetics (PK).
View Article and Find Full Text PDFSLCO1B1 Functional Variants, Bilirubin, Statin-Induced Myotoxicity, and Recent Sub-Saharan African Ancestry: A Precision Medicine Health Equity Study.
Clin Pharmacol Ther
March 2025
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.
Statin pharmacogenetic implementation guidelines are derived from evidence of primarily Eurocentrically biased study populations. Functional SLCO1B1 variants that are rare in these study populations have not been equitably investigated and are thus missing from guidelines. The objective of this precision medicine health equity study was to determine the clinical validity of understudied candidate functional SLCO1B1 variants common in people with 1,000 Genomes sub-Saharan African superpopulation (1KG-AFR-like) genetic similarity.
View Article and Find Full Text PDFEXPRESS: Identification of genetic variations in μ opioid receptor in cats.
Mol Pain
March 2025
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
μ-opioid receptor (MOP) plays a critical role in mediating opioid analgesic effects. Genetic variations, particularly those in the MOP gene (), significantly influence individual variations in opioid efficacy and side effects across species, highlighting the need for pharmacogenomic research in human and veterinary contexts. This study aimed to identify single-nucleotide variations (SNVs) within in 100 cats of various breeds.
View Article and Find Full Text PDFDolutegravir and Risk of Neuropsychiatric Adverse Events: a Pharmacogenetic Study.
J Infect Dis
February 2025
Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Dolutegravir treatment can lead to neuropsychiatric adverse events (NPAE). This study assessed the association between NPAE and polymorphisms in dolutegravir-related pharmacogenes, determined by next-generation sequencing panel testing. Using a case-control design, 36 patients having previously discontinued dolutegravir due to NPAE were compared to 98 patients tolerating dolutegravir.
View Article and Find Full Text PDFExploring Potential Drug Targets in Multiple Cardiovascular Diseases: A Study Based on Proteome-Wide Mendelian Randomization and Colocalization Analysis.
Cardiovasc Ther
March 2025
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
Cardiovascular diseases (CVDs) encompass a group of diseases that affect the heart and/or blood vessels, making them the leading cause of global mortality. In our study, we performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel therapeutic protein targets for CVDs and evaluate the potential drug-related protein side effects. We conducted a comprehensive proteome-wide MR study to assess the causal relationship between plasma proteins and the risk of CVDs.
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