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Therapeutic Drug Monitoring Apr 2019Although the monitoring of drug therapies based on the determination of drug concentrations in biological materials is certainly an important instrument for...
Although the monitoring of drug therapies based on the determination of drug concentrations in biological materials is certainly an important instrument for individualized dosing and dose adjustment with a broad variety of pharmaceuticals, its role is limited by the fact that it does not reflect pharmacodynamic (PD) and toxicodynamic interactions such as those caused by individual and environment-related factors. However, these interactions are important for both the efficacy and the safety of the drug therapy. Therefore, during recent years, there is an increased interest in personalized drug therapy as reflected by the development and clinical implementation of molecular "biomarkers" that are direct or surrogate markers of pharmacological effects [PD therapeutic drug monitoring (TDM)]. Moreover, this process is driven by new developments in instrumentation, such as mass spectrometry and array technologies, and in computational biology/pharmacology, databases, and bioinformatics. This Focus Issue of the journal focuses on current achievements in and status of PD TDM with different classes of drugs. The contributions to the present issue of Therapeutic Drug Monitoring provide a critical analysis of current practices of TDM with their limitations, introduce newer promising biomarkers in the field of PD TDM, discuss the challenges faced to date in translating preclinical tools into clinical settings, and point out recent advances in the establishment of modeling approaches that apply to pharmacokinetics (PK)/PD as well as pharmacogenetic information.
Topics: Biomarkers; Drug Monitoring; Humans; Pharmacology
PubMed: 30883504
DOI: 10.1097/FTD.0000000000000627 -
British Journal of Clinical Pharmacology Nov 2007
Topics: Drug Approval; Humans; Pharmacology
PubMed: 17935601
DOI: 10.1111/j.1365-2125.2007.03058.x -
Basic & Clinical Pharmacology &... May 2019Toxicological and pharmacological information from human cells and tissues provides knowledge readily applicable to human safety assessment and to the efficacy... (Review)
Review
Toxicological and pharmacological information from human cells and tissues provides knowledge readily applicable to human safety assessment and to the efficacy assessment of pharmaceuticals. The 3R principle in animal studies includes the use of human material in the R of Replacement. The Reduction and Refinement Rs are related to animal use. Knowledge of the 3Rs and successful 3R methods are a prerequisite for the Reduction of animal experiments in the future. More collaboration among researchers using experimental animals and those working in vitro is necessary with mutual respect. The OECD Guidelines for the Testing of Chemicals have included the animal-free part of the 3Rs in guidances for the development and reporting of Adverse Outcome Pathways (AOPs), which is to be part of the Integrated Approaches to Testing and Assessment (IATA). The 3R centres established to help fulfil the Directive 2010/63/EU play an important role to promote the 3Rs and in the development of animal-free toxicology. Research centres in each Nordic country are founded upon solid research activities in cell and organ toxicity, including major EU programmes to promote 3Rs and implementation of good practices and methods broadly in all stakeholders of industry, regulators and academia. In the light of this, the Nordic Symposium on Toxicology and Pharmacology without Animal Experiments addressed more adopted/modified test guidelines or new test guidelines for new end-points, or hazard challenges, new in vitro 3D models, speeding up transfer of knowledge from research to regulation to understand AOP and towards IATA.
Topics: Animal Experimentation; Animals; Drug Evaluation, Preclinical; Pharmacology; Scandinavian and Nordic Countries; Toxicology
PubMed: 30561843
DOI: 10.1111/bcpt.13193 -
Clinical Pharmacology and Therapeutics Jul 2015The scaling up of data in clinical pharmacology and the merger of systems biology and pharmacology has led to the emergence of a new discipline of Quantitative and... (Review)
Review
The scaling up of data in clinical pharmacology and the merger of systems biology and pharmacology has led to the emergence of a new discipline of Quantitative and Systems Pharmacology (QSP). This new research direction might significantly advance the discovery, development, and clinical use of therapeutic drugs. Research communities from computational biology, systems biology, and biological engineering--working collaboratively with pharmacologists, geneticists, biochemists, and analytical chemists--are creating and modeling large data on drug effects that is transforming our understanding of how these drugs work at a network level. In this review, we highlight developments in a new and rapidly growing field--pharmacometabolomics--in which large biochemical data-capturing effects of genome, gut microbiome, and environment exposures is revealing information about metabotypes and treatment outcomes, and creating metabolic signatures as new potential biomarkers. Pharmacometabolomics informs and complements pharmacogenomics and together they provide building blocks for QSP.
Topics: Biomarkers; Biomarkers, Pharmacological; Drug Discovery; Humans; Metabolic Networks and Pathways; Metabolome; Pharmacogenetics; Pharmacology; Phenotype; Precision Medicine
PubMed: 25871646
DOI: 10.1002/cpt.134 -
Clinical Pharmacology and Therapeutics Nov 2012Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the...
Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.
Topics: Cooperative Behavior; Drug Design; Humans; Periodicals as Topic; Pharmacology; Pharmacology, Clinical; Publishing; Societies, Pharmaceutical; United States
PubMed: 23085873
DOI: 10.1038/clpt.2012.151 -
Pharmacological Reviews Apr 2020Technology in bioanalysis, , and computation have evolved over the past half century to allow for comprehensive assessments of the molecular to whole body pharmacology... (Review)
Review
Technology in bioanalysis, , and computation have evolved over the past half century to allow for comprehensive assessments of the molecular to whole body pharmacology of diverse corticosteroids. Such studies have advanced pharmacokinetic and pharmacodynamic (PK/PD) concepts and models that often generalize across various classes of drugs. These models encompass the "pillars" of pharmacology, namely PK and target drug exposure, the mass-law interactions of drugs with receptors/targets, and the consequent turnover and homeostatic control of genes, biomarkers, physiologic responses, and disease symptoms. Pharmacokinetic methodology utilizes noncompartmental, compartmental, reversible, physiologic [full physiologically based pharmacokinetic (PBPK) and minimal PBPK], and target-mediated drug disposition models using a growing array of pharmacometric considerations and software. Basic PK/PD models have emerged (simple direct, biophase, slow receptor binding, indirect response, irreversible, turnover with inactivation, and transduction models) that place emphasis on parsimony, are mechanistic in nature, and serve as highly useful "top-down" methods of quantitating the actions of diverse drugs. These are often components of more complex quantitative systems pharmacology (QSP) models that explain the array of responses to various drugs, including corticosteroids. Progressively deeper mechanistic appreciation of PBPK, drug-target interactions, and systems physiology from the molecular (genomic, proteomic, metabolomic) to cellular to whole body levels provides the foundation for enhanced PK/PD to comprehensive QSP models. Our research based on cell, animal, clinical, and theoretical studies with corticosteroids have provided ideas and quantitative methods that have broadly advanced the fields of PK/PD and QSP modeling and illustrates the transition toward a global, systems understanding of actions of diverse drugs. SIGNIFICANCE STATEMENT: Over the past half century, pharmacokinetics (PK) and pharmacokinetics/pharmacodynamics (PK/PD) have evolved to provide an array of mechanism-based models that help quantitate the disposition and actions of most drugs. We describe how many basic PK and PK/PD model components were identified and often applied to the diverse properties of corticosteroids (CS). The CS have complications in disposition and a wide array of simple receptor-to complex gene-mediated actions in multiple organs. Continued assessments of such complexities have offered opportunities to develop models ranging from simple PK to enhanced PK/PD to quantitative systems pharmacology (QSP) that help explain therapeutic and adverse CS effects. Concurrent development of state-of-the-art PK, PK/PD, and QSP models are described alongside experimental studies that revealed diverse CS actions.
Topics: Adrenal Cortex Hormones; Animals; Computational Biology; Humans; Models, Biological; Pharmacokinetics; Pharmacology
PubMed: 32123034
DOI: 10.1124/pr.119.018101 -
Indian Journal of Pharmacology Oct 2016Competency-based medical education (CBME) is gaining momentum across the globe. The Medical Council of India has described the basic competencies required of an Indian... (Review)
Review
Competency-based medical education (CBME) is gaining momentum across the globe. The Medical Council of India has described the basic competencies required of an Indian Medical Graduate and designed a competency-based module on attitudes and communication. Widespread adoption of a competency-based approach would mean a paradigm shift in the current approach to medical education. CBME, hence, needs to be reviewed for its usefulness and limitations in the Indian context. This article describes the rationale of CBME and provides an overview of its components, i.e., competency, entrustable professional activity, and milestones. It elaborates how CBME could be implemented in an institute, in the context of basic sciences in general and pharmacology in particular. The promises and perils of CBME that need to be kept in mind to maximize its gains are described.
Topics: Competency-Based Education; Curriculum; Education, Medical; Humans; Pharmacology
PubMed: 28031599
DOI: 10.4103/0253-7613.193312 -
Pharmacological Research Dec 2016
Topics: Animals; Dopamine Agonists; Dopamine Antagonists; Drug Discovery; Humans; Pharmacology; Retinal Degeneration; Systems Analysis
PubMed: 27720767
DOI: 10.1016/j.phrs.2016.09.026 -
Journal of Lipid Research Jan 2016
Topics: Humans; Kinetics; Models, Biological; Pharmacology; Systems Biology
PubMed: 26590172
DOI: 10.1194/jlr.C065482 -
Physiological Research Jun 2018On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died from complications following surgery, only four years after retiring from the University of...
On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died from complications following surgery, only four years after retiring from the University of Bern. Trained in biochemistry at Oxford University, Sid had quickly moved into molecular pharmacology and became a key investigator in the field of enzyme biochemistry, vasoactive peptide research, and receptor signaling. Sid spent half his life in Switzerland, after moving to the University of Bern in 1984. This article, written by his friends and colleagues who knew him and worked with him during different stages of his career, summarizes his life, his passions, and his achievements in biomedical research. It also includes personal memories relating to a dear friend and outstanding scientist whose intellectual curiosity, humility, and honesty will remain an example to us all.
Topics: Biochemistry; Endothelins; England; History, 20th Century; History, 21st Century; Neuropharmacology; Pharmacology; Switzerland
PubMed: 31774298
DOI: No ID Found