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Clinical Pharmacology and Therapeutics Sep 2022
Topics: Humans; Membrane Transport Proteins; Pharmacokinetics; Pharmacology; Pharmacology, Clinical
PubMed: 35989454
DOI: 10.1002/cpt.2710 -
Journal of Pharmaceutical Sciences Jan 2024This review will highlight portions of Dr. William Jusko's and colleagues' work that affected the clinical use and study of corticosteroids in acute and chronic disease... (Review)
Review
This review will highlight portions of Dr. William Jusko's and colleagues' work that affected the clinical use and study of corticosteroids in acute and chronic disease management. Selected publications related to corticosteroid pharmacokinetics and pharmacodynamics from the 1970s through today were included in this review, with a focus on the foundational human-based studies conducted in the 1970s-1990s. Dr. Jusko contributed significantly to early corticosteroid pharmacology across several domains including: 1) foundational corticosteroid pharmacokinetic methods and parameter development, 2) disease state-variation in corticosteroid pharmacokinetics, 3) drug interaction effects on corticosteroid pharmacokinetics, and 4) early corticosteroid pharmacodynamic studies. In an era where little was known about the pharmacokinetics and pharmacodynamics of corticosteroids, Dr. Jusko's work opened the eyes of researchers and clinicians to the potential for disease and drug interactions that could reduce or enhance the effects of corticosteroids. This significant body of work paved the way for alternative routes of administration that would be useful in concentrating the activity at the site of action and markedly reduced systemic drug exposure, minimizing the risk of adverse effects through application of the dose-sparing pharmacokinetic and pharmacodynamic principles.
Topics: Humans; Adrenal Cortex Hormones; Drug Interactions; Pharmacology, Clinical
PubMed: 37844761
DOI: 10.1016/j.xphs.2023.10.016 -
International Journal of Molecular... Mar 2023Life is chiral, as its constituents consist, to a large degree, of optically active molecules, be they macromolecules (proteins, nucleic acids) or small biomolecules.... (Review)
Review
Life is chiral, as its constituents consist, to a large degree, of optically active molecules, be they macromolecules (proteins, nucleic acids) or small biomolecules. Hence, these molecules interact disparately with different enantiomers of chiral compounds, creating a preference for a particular enantiomer. This chiral discrimination is of special importance in medicinal chemistry, since many pharmacologically active compounds are used as racemates-equimolar mixtures of two enantiomers. Each of these enantiomers may express different behaviour in terms of pharmacodynamics, pharmacokinetics, and toxicity. The application of only one enantiomer may improve the bioactivity of a drug, as well as reduce the incidence and intensity of adverse effects. This is of special significance regarding the structure of natural products since the great majority of these compounds contain one or several chiral centres. In the present survey, we discuss the impact of chirality on anticancer chemotherapy and highlight the recent developments in this area. Particular attention has been given to synthetic derivatives of drugs of natural origin, as naturally occurring compounds constitute a major pool of new pharmacological leads. Studies have been selected which report the differential activity of the enantiomers or the activities of a single enantiomer and the racemate.
Topics: Humans; Chemistry, Pharmaceutical; Drug-Related Side Effects and Adverse Reactions; Stereoisomerism
PubMed: 36982753
DOI: 10.3390/ijms24065679 -
Vestnik Oftalmologii 2019In recent years, β-adrenergic blockers have become the first choice drugs for glaucoma treatment. Timolol holds the main position among them, being a part of most...
In recent years, β-adrenergic blockers have become the first choice drugs for glaucoma treatment. Timolol holds the main position among them, being a part of most combined antiglaucoma preparations. The use of timolol maleate in clinical practice may be accompanied by severe side effects affecting different organs and systems. The fact that cells with β-adrenergic receptors are widely common within the human body explains pharmacodynamic effects of timolol maleate. Because of these undesirable side effects, timolol maleate often evokes negative reaction from doctors and patients, which to certain extent limits its usage in ophthalmological practice. Obviously, efficacy and safety of timolol administration depends on individual characteristics making personalized approach necessary for every patient. Such particular approach, being the foundation of personalized medicine, increases efficacy and safety of timolol while reducing costs by using targeted doses.
Topics: Adrenergic beta-Antagonists; Humans; Intraocular Pressure; Pharmacogenetics; Timolol
PubMed: 31393458
DOI: 10.17116/oftalma2019135031137 -
Expert Opinion on Drug Metabolism &... May 2019The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also... (Review)
Review
The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic benefit and minimise patient harm Areas covered: This review article outlines the pharmacokinetic and pharmacodynamic profiles of the currently licensed VKAs and NOACs that are most commonly used in clinical practice, with the aim of demonstrating how variations in these characteristics influence their use in clinical practice. A literature search was conducted on PubMed using keywords and relevant articles published by the 31 of December 2018 were included. Expert opinion: The effect of a drug is determined by a combination of elements which include patient characteristics and external factors, in addition to its pharmacokinetic and pharmacodynamic properties. A good understanding of these is essential. Despite the wealth of information available, particularly on VKAs, our knowledge on the pharmacology responsible for certain drug effects and inter-individual variations is still limited. Increasing efforts are being made to understand these and include focus on pharmacogenomics and drug transporter proteins.
Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Humans; Membrane Transport Proteins; Pharmacogenetics; Vitamin K
PubMed: 30951640
DOI: 10.1080/17425255.2019.1604686 -
Clinical Pharmacology and Therapeutics Oct 2021Low- and middle-income countries (LMICs) have the highest rates of mortality and morbidity globally, but lag behind high-income countries in the number of clinical... (Review)
Review
Low- and middle-income countries (LMICs) have the highest rates of mortality and morbidity globally, but lag behind high-income countries in the number of clinical trials and trained researchers, as well as research data pertaining to their populations. Lack of local clinical pharmacology and pharmacometrics expertise, limited training opportunities, and lack of local genomic data may contribute to health inequalities and limit the application of precision medicine. Continuing to develop health care infrastructure, including well-designed clinical pharmacology training and data collection in LMICs, can help address these challenges. International collaboration aimed at improving training and infrastructure and encouraging locally driven research and clinical trials will be of benefit. This review describes several examples where clinical pharmacology expertise could be leveraged, including opportunities for pharmacogenomic expertise that could drive improved recommendations for clinical guidelines. Also described are clinical pharmacology and pharmacometrics training programs in Africa, and the personal experience of a Tanzanian researcher currently on a training sabbatical in the United States, as illustrative examples of how training in clinical pharmacology can be effectively implemented in LMICs. These training efforts will benefit from advocacy for employment opportunities and career development pathways for clinical pharmacologists that are gradually being recognized and developed in LMICs. Clinical pharmacologists have a key role to play in global health, and development of training and research infrastructure to advance this expertise in LMICs will be of tremendous benefit.
Topics: Biomedical Research; Career Choice; Career Mobility; Clinical Trials as Topic; Developing Countries; Global Health; Humans; Pharmacogenetics; Pharmacology, Clinical
PubMed: 33893656
DOI: 10.1002/cpt.2274 -
Trends in Biotechnology Dec 2018Chemical probes represent versatile tools to validate disease-modifying targets. However, evaluating the selectivity of chemical probes in complex cellular systems is a... (Review)
Review
Chemical probes represent versatile tools to validate disease-modifying targets. However, evaluating the selectivity of chemical probes in complex cellular systems is a major challenge that needs to be addressed to better understand the mode of action of small molecules and the interpretation of their pharmacological effects. Chemoproteomics has emerged as a key technology to characterize the mode of action of pharmacological modulators such as chemical probes and drugs, and these studies have unraveled the cellular targets of many bioactive compounds. Here we review the role of chemical probes for the validation of new therapeutic targets and their characterization by proteome wide affinity- and activity-based chemical proteomics and recently developed label-free technologies.
Topics: Drug Discovery; Pharmacology; Proteome; Proteomics
PubMed: 30017093
DOI: 10.1016/j.tibtech.2018.06.008 -
International Journal of Pharmaceutics Aug 2018Cocrystals are homogenous (single-phase) crystalline structures composed by two or more components in a definite stoichiometric ratio bonded together by noncovalent... (Review)
Review
Cocrystals are homogenous (single-phase) crystalline structures composed by two or more components in a definite stoichiometric ratio bonded together by noncovalent bonds. Pharmaceutical industry has been showing interest in cocrystals due to their ability to improve active pharmaceutical ingredients (API's) properties, such as solubility, dissolution, bioavailability, stability and processability. The necessity for high-throughput screening methods and methods capable of producing cocrystals in an industrial scale still hinders the use of cocrystals by the pharmaceutical industry. The aim of this review is to present an extensive overview of the cocrystallization methods, focusing in the specificities of each technique, its advantages and disadvantages. The review is divided into solvent-based and solvent-free methods. The most appropriate methods to the different stages of cocrystals manufacture, from the screening phase to industrial production are identified. The use of continuous and scalable methods in cocrystal production as well as the implementation of quality-by-design and process analytical technology concepts are also addressed.
Topics: Biological Availability; Chemistry, Pharmaceutical; Crystallization; Drug Compounding; High-Throughput Screening Assays; Pharmacology; Solubility; Solvents; X-Ray Diffraction
PubMed: 29890258
DOI: 10.1016/j.ijpharm.2018.06.024 -
Clinical Pharmacology and Therapeutics May 2023
Topics: Humans; Pharmacology, Clinical; Biomarkers; Pharmacology
PubMed: 37069736
DOI: 10.1002/cpt.2880 -
Clinical Pharmacology and Therapeutics Aug 2022
Topics: Humans; Pharmacology; Pharmacology, Clinical
PubMed: 35849717
DOI: 10.1002/cpt.2680