Incorporating receptor theory in mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling. (1/15)
Pharmacokinetic-Pharmacodynamic (PK-PD) modeling helps to better understand drug efficacy and safety and has, therefore, become a powerful tool in the learning-confirming cycles of drug-development. In translational drug research, mechanism-based PK-PD modeling has been recognized as a tool for bringing forward early insights in drug efficacy and safety into the clinical development. These models differ from descriptive PK-PD models in that they quantitatively characterize specific processes in the causal chain between drug administration and effect. This includes target site distribution, binding and activation, pharmacodynamic interactions, transduction and homeostatic feedback mechanisms. Compared to descriptive models mechanism-based PK-PD models that utilize receptor theory concepts for characterization of target binding and target activation processes have improved properties for extrapolation and prediction. In this respect, receptor theory constitutes the basis for 1) prediction of in vivo drug concentration-effect relationships and 2) characterization of target association-dissociation kinetics as determinants of hysteresis in the time course of the drug effect. This approach intrinsically distinguishes drug- and system specific parameters explicitly, allowing accurate extrapolation from in vitro to in vivo and across species. This review provides an overview of recent developments in incorporating receptor theory in PK-PD modeling with a specific focus on the identifiability of these models. (+info)Scaling pharmacodynamics from in vitro and preclinical animal studies to humans. (2/15)
An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses. (+info)A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: A tale of 'bottom-up' vs 'top-down' recognition of covariates. (3/15)
An increasing number of failures in clinical stages of drug development have been related to the effects of candidate drugs in a sub-group of patients rather than the 'average' person. Expectation of extreme effects or lack of therapeutic effects in some subgroups following administration of similar doses requires a full understanding of the issue of variability and the importance of identifying covariates that determine the exposure to the drug candidates in each individual. In any drug development program the earlier these covariates are known the better. An important component of the drive to decrease this failure rate in drug development involves attempts to use physiologically-based pharmacokinetics 'bottom-up' modeling and simulation to optimize molecular features with respect to the absorption, distribution, metabolism and elimination (ADME) processes. The key element of this approach is the separation of information on the system (i.e. human body) from that of the drug (e.g. physicochemical characteristics determining permeability through membranes, partitioning to tissues, binding to plasma proteins or affinities toward certain enzymes and transporter proteins) and the study design (e.g. dose, route and frequency of administration, concomitant drugs and food). In this review, the classical 'top-down' approach in covariate recognition is compared with the 'bottom-up' paradigm. The determinants and sources of inter-individual variability in different stages of drug absorption, distribution, metabolism and excretion are discussed in detail. Further, the commonly known tools for simulating ADME properties are introduced. (+info)Pharmacological changes in cellular Ca2+ homeostasis parallel initiation of atrial arrhythmogenesis in murine Langendorff-perfused hearts. (4/15)
(+info)Beyond thermodynamics: drug binding kinetics could influence epidermal growth factor signaling. (5/15)
(+info)Identifying druggable disease-modifying gene products. (6/15)
(+info)Non-genetic cell-to-cell variability and the consequences for pharmacology. (7/15)
(+info)Inwardly rectifying potassium channels: their structure, function, and physiological roles. (8/15)
(+info)Pharmacological processes refer to the series of interactions and reactions that occur when a drug is introduced into a living organism. This encompasses various stages, including:
1. **Drug Absorption:** The process by which a drug is taken up by the body's tissues after administration, often through routes such as oral, intravenous, or topical.
2. **Distribution:** The movement of the drug throughout the body, often involving transport across biological membranes and into various organs and fluids.
3. **Metabolism (Biotransformation):** The chemical alteration of a drug by enzymes, primarily in the liver but also in other organs, which can result in the drug becoming more or less active, or being broken down into products that can be excreted.
4. **Excretion:** The removal of the drug and its metabolites from the body, typically through urine, feces, sweat, or exhaled air.
5. **Pharmacodynamics:** The study of how drugs interact with their targets (receptors, enzymes, etc.) to produce a biological response.
6. **Pharmacokinetics:** The mathematical analysis of the time course of drug concentrations in the body and how these concentrations affect pharmacological responses.
Understanding these pharmacological processes is crucial for determining the optimal dosage, frequency, and route of administration for a drug, as well as predicting potential interactions and side effects.
Benfotiamine
Tropomyosin receptor kinase B
Brain-derived neurotrophic factor
4-Hydroxy-TEMPO
Hydroxytyrosol
Georges Chapouthier
Focal infection theory
Annexin A1
Biology of depression
Actoprotector
Benjamin Weiss (scientist)
Scott A. Small
Pharmacokinetics of progesterone
Subjective report
Oligonucleotide
Eosinophilic esophagitis
Hyphomycetes
Bulimia nervosa
Phylogenetics
Coicenal
Traumatic memories
Pseudophobia
N-Acylethanolamine
2,5-Dimethoxy-4-propylamphetamine
Aggresome
Uterotonic
Medicina Plinii
Cognitive processing therapy
Methoctramine
Voltage-sensitive dye
Prodrug
Review of Natural Language Processing in Pharmacology | Pharmacological Reviews
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Pharmacological Treatments to Prevent COPD Exacerbations
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NLM Classification 2012 Edition. NLM Technical Bulletin. 2012 May-Jun
Benfotiamine - Wikipedia
Pharmacological chaperones stabilize retromer to limit APP processing. | Helen & Robert Appel Alzheimer's Disease Research...
Poon - Apoptotic cell disassembly and clearance
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Non-pharmacological interventions for autism spectrum disorder in children: an overview of systematic reviews | BMJ Evidence...
PDF) PHARMACOLOGICAL ACTIVITY OF SPINACIA OLERACEA LINN.
Science Clips - Volume 10, Issue 18, May 22, 2018
Frontiers | Pharmacological Tuning of Adenosine Signal Nuances Underlying Heart Failure With Preserved Ejection Fraction
Stand Alone Modules | School of Nursing and Midwifery | Queen's University Belfast
Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms | Scientific Reports
Primary care patients' perspectives on the use of non-pharmacological home remedies in Geneva: a cross-sectional study | BMC...
Precision Medicine and Pharmacological Innovation | Postgraduate Taught Subjects | Study Here | The University of Aberdeen
Love and addiction: the devil is in the differences: a commentary on "The behavioral, anatomical and pharmacological parallels...
A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy | Nature Communications
PA-11-034: Functional Genetics, Epigenetics, and Non-coding RNAs in Drug Addiction (R21)
Metabolism and pharmacological activities of the natural health-benefiting compound diosmin - Food & Function (RSC Publishing)
Pharmacodynamic Biomarkers: Their Role in Biosimilar Product Development | FDA
Jazwinska Group | Department of Biology | University of Fribourg
Recommendations | Generalised anxiety disorder and panic disorder in adults: management | Guidance | NICE
Interventions1
- Hyperarousal, that is, a state of heightened alertness and disinhibition, as a core feature of misophonia is supported by behavioral and neuroimaging literature and might represent a viable clinical target for the development of both behavioral and pharmacological interventions. (lu.se)
Genetic3
- Our lab studies the roles of lipid biosynthesis in this process, using pharmacological, genetic, and molecular approaches. (csun.edu)
- Our lab combines multimodal brain imaging, opto-chemogenetics, electrophysiology and quantitative modelling to investigate the neural drivers of large-scale brain connectivity, and its modulation by genetic, pathological or pharmacological effectors. (fens.org)
- Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterial s through genetic or pharmacological manipulations. (cdc.gov)
Clinical9
- To examine the current ethical review process (ERP) of ethics committees in a non-pharmacological trial from the perspective of a clinical investigator. (bmj.com)
- Based on metabolic theories of Alzheimer's disease, since thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of Alzheimer's disease patients at autopsy, and since treatment of mouse models of Alzheimer's disease with benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits, benfotiamine administration has been proposed as a possible intervention to reverse biological and clinical processes of Alzheimer's disease. (wikipedia.org)
- Raw CO (rCO) and wine -processed CO (pCO), the main processed products of CO for clinical application, show differences in nourishing kidney yang and ameliorate osteoporosis . (bvsalud.org)
- In conclusion, this study first investigated the chemical composition and potential pharmacological effects of the main chemical compounds in QZC, which will contribute to the revelation of bioactive compounds in QZC and provide evidence for clinical application. (hindawi.com)
- Preclinical to clinical translation shows the importance of pharmacology in the drug discovery/development process. (bps.ac.uk)
- This review provides an overview of their structural simplicity, precursor processing, biological activities and evolution, and sheds insight into their potential clinical and agricultural applications. (nih.gov)
- They assert that the contribution to preventable deaths by a diet dominated by highly processed foods is comparable to that of tobacco products, and as such, like Unwin, the authors seek clinical recognition and a more formalized protocol to manage food addiction. (medscape.com)
- Anxiety patients were used as a clinical control group to distinguish attentional processes specific for misophonia. (lu.se)
- Over the past three decades, clinical and pharmacological studies have accumulated a body of evidence that not only demonstrated these therapeutic effects, but also provided significant insights into the pharmacokinetic behavior, therapeutic profile, and mode of action of scutellarin in humans and animal models. (cdc.gov)
Mechanism of act2
- Recognised the team at Vertex Pharmaceuticals responsible for the development of lumacraftor/ivacaftor, based on a novel, innovative pharmacological mechanism of action and treating a significant unmet medical need in patients suffering from Cystic Fibrosis. (bps.ac.uk)
- Here we review the current literature on scutellarin to provide a comprehensive understanding of the pharmacological activity, mechanism of action, toxicity, and therapeutic potential of scutellarin for the treatment of ischemia, diabetic complications, and other chronic diseases. (cdc.gov)
Behavioral1
- Love and addiction: the devil is in the differences: a commentary on "The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction. (springer.com)
Receptor2
- An endogenous substance or a drug that can interact with a receptor and initiate a physiological or a pharmacological response characteristic of that receptor (contraction, relaxation, secretion, enzyme activation, etc. (genomicglossaries.com)
- Ion channel modulation by general anesthetics is a vital pharmacological process with implications for receptor biophysics and drug development. (rcsb.org)
Treatments2
- Effective pharmacological and non-pharmacological treatments remain elusive. (iasp-pain.org)
- Psychological versus pharmacological treatments of bulimia nervosa: predictors and processes of change. (bvsalud.org)
Molecular2
- These work by intercepting the inflammatory process at the molecular level. (reportlinker.com)
- In addition, the molecular function of some of the described proteins suggests a central role for SVEVs in the cytotoxicity of the snake venom and sheds new light in the envenomation process. (nature.com)
Perspective2
- Obstetric nurses' perspective: use of non-pharmacological methods for the relief of labor pain. (bvsalud.org)
- To understand the perspective of obstetric nurses on the use of non- pharmacological methods for the relief of labor pain. (bvsalud.org)
Therapeutic1
- Study means to speed up the process of making newly selected INN known to the public before the "official publication", through a preliminary publication of a reduced set of data on the Web (e.g., including only the proposed INN and a statement on the pharmacological action and therapeutic use of the substance in question). (who.int)
Psychological1
- Dr. Cohen's research concerns the psychological processes underlying ideological extremism and violence on both the interpersonal and international levels. (cuny.edu)
Chemical2
- A chemical or pharmacological stress test uses a medication that increases your heart load in the place of exercise. (dignityhealth.org)
- The degree has an engaging and dynamic curriculum that deals with the underpinning science of the drug development process, including physical, chemical and biological concepts. (qub.ac.uk)
Therapy2
- A greater understanding of detrusor physiology as well as the development of effective drugs for solving the dynamic and static components of the obstruction in the prostate and bladder neck have paved the path for the ubiquity of pharmacological therapy for BPH. (medscape.com)
- Pharmacological BPH therapy protocols advocate the use of α-blockers (ABs) and 5α-reductase inhibitors (5ARI), individually or in combination, as well as phosphodiesterase-5 (PDE5) inhibitors, individually or concomitantly with ABs. (medscape.com)
Paradigm1
- Allergy follows to a certain extent the pharmacological/toxicological paradigm of dose-response relationship. (cdc.gov)
Approaches1
- Our methods rely on pharmacological approaches and transgenic animals. (unifr.ch)
Modulation1
- The Functional Neuroimaging laboratory at the Istituto Italiano di Tecnologia ( https://www.fnimg.iit.it/ ), Rovereto (Italy), invites applications for an industrially funded PhD scholarship aimed at investigating pharmacological modulation of brain connectivity in the mammalian brain. (fens.org)
Initiate1
- These proteins are responsible for inducing several pharmacological effects aiming to immobilize and initiate the pre-digestion of the prey. (nature.com)
Proven1
- Besides, all these compounds were proven to have potential pharmacological activity in the treatment of RA based on network pharmacology analysis. (hindawi.com)
Approach1
- By a broad mass spectrometry based approach on whole cells we are in the process of identifying additional such proteins and their phosphorylation status. (lu.se)
Critical1
- The nutrient signaling pathways are coupled to cellular processes, and the cross-talk between the two is critical in maintaining a well-balanced systemic function of the body. (standardprocess.com)
Innovative1
- Innovative pharmacological solutions continuously redefine psoriatic arthritis treatment. (reportlinker.com)
Effects1
- Unlike effects of pharmacologically and toxicologically active substances, allergens elicit their adverse effects in a two-stage process. (cdc.gov)
Research2
- Our BSc degree course in Pharmaceutical Sciences is designed to create the next generation of pharmaceutical scientists, able to work in all stages of the drug development process as part of a multi-disciplinary research team. (qub.ac.uk)
- The project will be at the intersection of pharmacological neuroscience and brain imaging, and will entail multiple shared research, as well as secondments at the headquarters of an industrial partner. (fens.org)
Diseases1
- The potential impact of citron and its bioactive components to prevent or reverse destructive deregulated processes responsible for certain diseases has attracted different researchers' attention. (rsc.org)
Diet1
- Physiological manifestations like stress, and poor diet may negatively impact other systems in the body via specific cellular processes. (standardprocess.com)
Targets1
- Processing of the oxytocin molecule and its targets. (aspetjournals.org)
Inflammatory process1
- Hemp oil and omega-3 oil may support the resolution phase of the inflammatory process by providing PUFAs which are known to be precursors to endocannabinoids. (standardprocess.com)
Addiction2
- This suggests that the changes in D1R following pair bonding are induced via mechanisms that are independent of addiction-related processes. (springer.com)
- LONDON - Highly processed foods meet the same criteria as tobacco for addiction, and labeling them as such might benefit public health, according to a new US study that proposes a set of criteria to assess the addictive potential of some foods. (medscape.com)
Activities2
Systemic1
- How do systemic factors modulate this process? (unifr.ch)
Stress1
- A pharmacological stress test is done when an exercise stress test is not possible due to physical limitations like back trouble, joint disease, prior stroke, dizziness or shortness of breath. (dignityhealth.org)
Metabolic1
- The ECS regulates nearly every metabolic process in the body system. (standardprocess.com)
Potential1
- Meanwhile, the authors of the US study, led by Ashley N. Gearhardt, PhD, a psychologist from the University of Michigan, Ann Arbor, write that the ability of highly processed foods (HPFs) "to rapidly deliver high doses of refined carbohydrates and/or fat appear key to their addictive potential. (medscape.com)
Target1
- To target hypoglossal motoneurons with simultaneous pharmacological and optical stimuli we used customized "opto-dialysis" probes and chronically implanted them in mice expressing a light sensitive cation channel exclusively on cholinergic neurons (ChAT-ChR2, n = 12) and wild-type mice lacking the opsin (n = 10). (nature.com)
Content1
- The administrative process has to be standardised: the application forms and the number and content of the documents required should be identical or at least similar. (bmj.com)
Management1
- The update will focus on pharmacological management of chronic heart failure. (nice.org.uk)
Technology1
- With the assistance of the INN Expert Group, study the feasibility of means to speed up the selection process, including the possibility for more meetings, using modern technology, for example, electronic voting and teleconferences. (who.int)
Selection process2
- Final admission to the doctoral school entails a competitive selection process, as per the doctoral school regulations. (fens.org)
- Any interested party can informally contact Dr Alessandro Gozzi ([email protected]) to gather more information about the position, the project and the selection process. (fens.org)