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Evaluation of stabilizing additives to protect activities of cytochrome P450 enzymes for in vitro drug testing and pharmacogenetic studies: Focus on CYP2D6.
Biochim Biophys Acta Gen Subj
January 2025
Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany.
In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell models and organoids, offer promising alternatives but may not fully replicate physiological processes, especially for Cytochrome P450 (CYP) families involved in extrahepatic metabolism.
View Article and Find Full Text PDFPharmacogenetic Testing for Predicting Methylphenidate Treatment Outcomes in Childhood Attention Deficit Hyperactivity Disorder in Turkey: Focus on Carboxylesterase 1, Latrophilin-3, and Catechol-O-Methyltransferase.
Am J Med Genet B Neuropsychiatr Genet
January 2025
Biruni University Research Center (B@MER), Biruni University, Istanbul, Turkey.
Pharmacogenetic studies involving Carboxylesterase 1 (CES1), Latrophilin-3 (LPHN3), and Catechol-O-methyltransferase (COMT) revealed individual differences regarding therapeutic response in children with attention deficit hyperactivity disorder (ADHD) under methylphenidate (MPH) treatment. This study aimed to evaluate MPH's association with the adverse effect status in children and its relationship with CES1, LPHN3, and COMT in the Turkish population. The study included 102 children and adolescents with ADHD, who were categorized as responders, or the adverse effect group based on their treatment response.
View Article and Find Full Text PDFPharmacogenetic Testing in Admixed Populations: Frequency of the Association for Molecular Pathology Pharmacogenomics Working Group Tier 1 Variant Alleles in Brazilians.
J Mol Diagn
January 2025
Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil. Electronic address:
This article examines the frequency distribution of tier 1 pharmacogenetic variants of the Association for Molecular Pathology Pharmacogenomics Working Group Recommendations in two large (>1000 individuals) cohorts of the admixed Brazilian population, and in patients from the Brazilian Public Health System enrolled in pharmacogenetic trials. Three tier 1 variants, all in DPYD, were consistently absent, which may justify their noninclusion in genotyping panels for Brazilians; 13 variants had frequency ≤1.0%, and the remaining 21 variants ranged in frequency from 1.
View Article and Find Full Text PDFExploring the Pharmacogenomic Map of Croatia: PGx Clustering of 522-Patient Cohort Based on UMAP + HDBSCAN Algorithm.
Int J Mol Sci
January 2025
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia.
Pharmacogenetics is a branch of genomic medicine aiming to personalize drug prescription guidelines based on individual genetic information. This concept might lead to a reduction in adverse drug reactions, which place a heavy burden on individual patients' health and the economy of the healthcare system. The aim of this study was to present insights gained from the pharmacogenetics-based clustering of over 500 patients from the Croatian population.
View Article and Find Full Text PDFThe Rise of Fentanyl: Molecular Aspects and Forensic Investigations.
Int J Mol Sci
January 2025
Legal Medicine, Department of Medical, Surgical and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications.
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