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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 -
British Journal of Clinical Pharmacology Jan 2017
Topics: Biomedical Research; Diet Therapy; Dietary Supplements; Drug Therapy; Humans; Pharmacology; Preventive Medicine
PubMed: 27933660
DOI: 10.1111/bcp.13142 -
Clinical and Translational Science Oct 2022Pharmaceutical products in the current accelerated drug development landscape can benefit from tools beyond data generated from randomized control trials. We have seen... (Review)
Review
Pharmaceutical products in the current accelerated drug development landscape can benefit from tools beyond data generated from randomized control trials. We have seen an abundance of real-world data (RWD) and real-world evidence, driven by the digitalization of healthcare systems and an increased awareness that has inspired a heightened interest in their potential use. Literature review suggest leveraging RWD as a promising tool to answer key questions in the areas of clinical pharmacology and translational science. RWD may increase our understanding regarding the impact of intrinsic (e.g., liver, renal impairment, or genetic polymorphisms) and extrinsic (e.g., food consumption or concomitant medications) factors on the clearance of administered drugs. Changes in clearance may lead to clinically relevant changes in drug exposure that may require clinical management strategies, such as change in dose or dosing regimen. RWD can be leveraged to potentially bridge the gaps among research, development, and clinical care. This paper highlights promising areas of how RWD have been used to complement clinical pharmacology throughout various phases of drug development; case examples will include dose/regimen extrapolation, dose adjustments for special populations (organ impairment, pediatrics, etc.), and pharmacokinetic/pharmacodynamic models to assess impact of prognostic factors on outcomes. In addition, this paper will also juxtapose limitations and promises of utilizing RWD to answer key scientific questions in drug development and articulate challenges posed by quality issues, data availability, and integration from various sources as well as the increased need for multidimensional-omics data that can better guide the development of personalized and predictive medicine.
Topics: Humans; Child; Pharmacology, Clinical; Delivery of Health Care; Drug Development; Pharmaceutical Preparations
PubMed: 35912537
DOI: 10.1111/cts.13379 -
CPT: Pharmacometrics & Systems... Nov 2023
Topics: Humans; Network Pharmacology; Medical Oncology; Pharmacology, Clinical; Pharmacology
PubMed: 37849052
DOI: 10.1002/psp4.13066 -
Canadian Medical Association Journal Oct 1965The chemical structures and reactions of penicillins and cephalosporins are reviewed in relation to their effects upon pharmacodynamic properties. The reactive... (Review)
Review
The chemical structures and reactions of penicillins and cephalosporins are reviewed in relation to their effects upon pharmacodynamic properties. The reactive betalactam ring is common to all penicillins and cephalosporin C analogues. This ring opens during acylation of the bacterial wall-building enzymes, but previous opening of the ring by acid or beta-lactamases destroys antibiotic activity.Semisynthetic substitutions may protect the ring by steric hindrance; this may actually inactivate certain penicillinases, so that resistant penicillins may potentiate penicillin G in some circumstances. However, the protective substitutions reduce the intrinsic activity of the synthetic penicillins themselves. Other properties which are affected include absorption, protein-binding, excretion, and possible allergenicity of the drugs. Effects on antibacterial spectrum may possibly be secondary to alteration of lipid solubility.
Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical
PubMed: 5318573
DOI: No ID Found -
Small (Weinheim An Der Bergstrasse,... Jan 2018Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools...
Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported. The device integrates microscale inorganic light-emitting diodes and microfluidic drug delivery systems with a tiny stretchable multichannel radiofrequency antenna, which not only eliminates the need for bulky batteries but also offers fully wireless, independent control of light and fluid delivery. This design enables a miniature (125 mm ), lightweight (220 mg), soft, and flexible platform, thus facilitating seamless implantation and operation in the body without causing disturbance of naturalistic behavior. The proof-of-principle experiments and analytical studies validate the feasibility and reliability of the fully implantable optofluidic systems for use in freely moving animals, demonstrating its potential for wireless in vivo pharmacology and optogenetics.
Topics: Optogenetics; Pharmacology; Wireless Technology
PubMed: 29215787
DOI: 10.1002/smll.201702479 -
Pharmacology Research & Perspectives Dec 2021Pharmacology education currently lacks a research-based consensus on which core concepts all graduates should know and understand, as well as a valid and reliable means...
Pharmacology education currently lacks a research-based consensus on which core concepts all graduates should know and understand, as well as a valid and reliable means to assess core conceptual learning. The Core Concepts in Pharmacology Expert Group (CC-PEG) from Australia and New Zealand recently identified a set of core concepts of pharmacology education as a first step toward developing a concept inventory-a valid and reliable tool to assess learner attainment of concepts. In the current study, CC-PEG used established methodologies to define each concept and then unpack its key components. Expert working groups of three to seven educators were formed to unpack concepts within specific conceptual groupings: what the body does to the drug (pharmacokinetics); what the drug does to the body (pharmacodynamics); and system integration and modification of drug-response. First, a one-sentence definition was developed for each core concept. Next, sub-concepts were established for each core concept. These twenty core concepts, along with their respective definitions and sub-concepts, can provide pharmacology educators with a resource to guide the development of new curricula and the evaluation of existing curricula. The unpacking and articulation of these core concepts will also inform the development of a pharmacology concept inventory. We anticipate that these resources will advance further collaboration across the international pharmacology education community to improve curricula, teaching, assessment, and learning.
Topics: Australia; Cooperative Behavior; Curriculum; Humans; Learning; New Zealand; Pharmacology; Teaching
PubMed: 34817122
DOI: 10.1002/prp2.894 -
British Journal of Clinical Pharmacology Jun 2012Historically, much drug discovery and development in psychopharmacology tended to be empirical. However, over the last 20 years it has primarily been target oriented,... (Review)
Review
Historically, much drug discovery and development in psychopharmacology tended to be empirical. However, over the last 20 years it has primarily been target oriented, with synthesis and selection of compounds designed to act at a specific neurochemical site. Such compounds are then examined in functional animal models of disease. There is little evidence that this approach (which we call 'targetophilia') has enhanced the discovery process and some indications that it may have retarded it. A major problem is the weakness of many animal models in mimicking the disease and the lack of appropriate biochemical markers of drug action in animals and patients. In this review we argue that preclinical studies should be conducted as if they were clinical studies in design, analysis, and reporting, and that clinical pharmacologists should be involved at the earliest stages, to help ensure that animal models reflect as closely as possible the clinical disease. In addition, their familiarity with pharmacokinetic-pharmacodynamic integration (PK-PD) would help ensure that appropriate dosing and drug measurement techniques are applied to the discovery process, thereby producing results with relevance to therapeutics. Better integration of experimental and clinical pharmacologists early in the discovery process would allow observations in animals and patients to be quickly exchanged between the two disciplines. This non-linear approach to discovery used to be the way research proceeded, and it resulted in productivity that has never been bettered. It also follows that occasionally 'look-see' studies, a proven technique for drug discovery, deserve to be reintroduced.
Topics: Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Humans; Models, Animal; Neuropharmacology; Pharmaceutical Preparations
PubMed: 22360689
DOI: 10.1111/j.1365-2125.2012.04246.x -
The Mount Sinai Journal of Medicine,... 2010The drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National... (Review)
Review
The drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National Institutes of Health Roadmap highlighting translational science and medicine. Because drug discovery and development represents a pipeline of basic to clinical investigations, it meshes well with the "bench to the bedside" prime directive of translational medicine. The renewed interest in drug discovery and development in academia provides an opportunity to rethink the hiearchary of studies with the hope of improving the staid approaches that have been criticized for lacking innovation. One area that has received limited attention concerns the use of pharmacokinetic and pharmacodynamic studies in the drug-development process. Using anticancer drug development as a focus, this review will address past and current deficencies in how pharmacokinetic/pharmacodynamic studies are conducted and offer new strategies that might bridge the gap between preclinical and clinical trials.
Topics: Antineoplastic Agents; Biomedical Research; Drug Design; Humans; Neoplasms; Pharmacogenetics; Pharmacokinetics; Pharmacological Phenomena; Precision Medicine; Translational Research, Biomedical
PubMed: 20687184
DOI: 10.1002/msj.20193 -
Journal of Lipid Research Jan 2016
Topics: Humans; Kinetics; Models, Biological; Pharmacology; Systems Biology
PubMed: 26590172
DOI: 10.1194/jlr.C065482