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Journal of Child and Adolescent... Oct 2023
Topics: Humans; Mental Disorders; Psychopharmacology
PubMed: 37861991
DOI: 10.1089/cap.2023.29248.editorial -
Clinical Laboratory Aug 2023Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. (Review)
Review
BACKGROUND
Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories.
METHODS
This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS).
RESULTS
Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants.
CONCLUSIONS
The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.
Topics: Humans; Pharmacogenetics; High-Throughput Nucleotide Sequencing
PubMed: 37560847
DOI: 10.7754/Clin.Lab.2023.230103 -
Therapie 2023
Topics: Humans; Pharmacoepidemiology; Product Surveillance, Postmarketing
PubMed: 36732138
DOI: 10.1016/j.therap.2023.01.001 -
Clinical Pharmacokinetics Oct 2023Imeglimin (PXL008, EMD-387008, Twymeeg) is a first-in-class novel oral hypoglycemic agent, launched in Japan, for the treatment of type 2 diabetes mellitus. Its... (Review)
Review
Imeglimin (PXL008, EMD-387008, Twymeeg) is a first-in-class novel oral hypoglycemic agent, launched in Japan, for the treatment of type 2 diabetes mellitus. Its mechanism of action targets mitochondrial bioenergetics to ameliorate insulin resistance and to enhance β-cell function. This review summarizes the properties underlying the pharmacokinetic profile of imeglimin, a small cationic drug belonging to the tetrahydrotriazine chemical class, with a complex mechanism of absorption involving an active transport through organic cation transporters (OCTs). Imeglimin absorption decreases when dose increases due to the saturation of the active uptake transport. Post absorption, imeglimin is rapidly and primarily distributed to organs and tissues, and has a half-life ranging from 9.03 to 20.2 h. Plasma protein binding of imeglimin is low, which explains the rapid distribution to the organs observed in all species. Imeglimin is excreted unchanged in urine, indicating a low extent of metabolism. Imeglimin is a substrate of multidrug and toxic compound extrusion (MATE) 2-K and a substrate and inhibitor of OCT1, OCT2, and MATE1. Clinical drug-drug interaction studies confirmed the absence of relevant clinical interaction with substrates or inhibitors of these transporters. Overall, the drug-drug interaction potential of imeglimin is low. Its pharmacokinetics profile has also been characterized in special populations, showing no influence of mild and moderate hepatic impairment but an impact of renal function on imeglimin renal clearance. Dosage adjustment is thus required in moderately and severely renally impaired patients. Imeglimin pharmacokinetics was shown to be insensitive to ethnicity and food intake and to have no effect on QTcF interval.
Topics: Humans; Diabetes Mellitus, Type 2; Pharmacology, Clinical; Biological Transport
PubMed: 37713097
DOI: 10.1007/s40262-023-01301-y -
Pharmacogenomics Jul 2023The field of psychiatry is facing an important paradigm shift in the provision of clinical care and mental health service organization toward personalization and...
The field of psychiatry is facing an important paradigm shift in the provision of clinical care and mental health service organization toward personalization and integration of multimodal data science. This approach, termed precision psychiatry, aims at identifying subgroups of patients more prone to the development of a certain phenotype, such as symptoms or severe mental disorders (risk detection), and/or to guide treatment selection. Pharmacogenomics and computational psychiatry are two fundamental tools of precision psychiatry, which have seen increasing levels of integration in clinical settings. Here we present a brief overview of these two applications of precision psychiatry in clinical settings.
Topics: Humans; Mental Disorders; Pharmacogenetics; Precision Medicine; Psychiatry
PubMed: 37458685
DOI: 10.2217/pgs-2023-0112 -
Molecular Pharmaceutics Dec 2023
Topics: Biopharmaceutics; Pharmacy; Drug Compounding
PubMed: 38044834
DOI: 10.1021/acs.molpharmaceut.3c01068 -
Clinical Pharmacology and Therapeutics Jul 2023
Topics: Humans; Pharmacology, Clinical; Pharmacology
PubMed: 37335056
DOI: 10.1002/cpt.2931 -
Annual Review of Pharmacology and... Jan 2024I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have... (Review)
Review
I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: () discovery and characterization of the AHR/CYP1 axis, () pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, () standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and () discovery and characterization of the gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.
Topics: Humans; Animals; Mice; Genomics; Membrane Transport Proteins; Pharmacogenetics; Physicians
PubMed: 37788491
DOI: 10.1146/annurev-pharmtox-022323-082311 -
Science (New York, N.Y.) Nov 2023Physician-scientist who discovered NO signaling.
Physician-scientist who discovered NO signaling.
Topics: Nitric Oxide; Nobel Prize; Signal Transduction; Physiology; Pharmacology, Clinical; United States
PubMed: 37917686
DOI: 10.1126/science.adl1754 -
The Journal of Pharmacology and... Aug 2023
Topics: Pharmacology, Clinical; Periodicals as Topic
PubMed: 37460160
DOI: 10.1124/jpet.123.001743