Abstract:
:Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interactions, transduction, and homeostatic feedback mechanisms. As the final step, the effects on disease processes and disease progression are considered. Particularly through the incorporation of concepts from receptor theory and dynamical systems analysis, important progress has been made in the field of mechanism-based PK-PD modeling. This has yielded models with much-improved properties for extrapolation and prediction. These models constitute a theoretical basis for rational drug discovery and development.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Danhof M,de Jongh J,De Lange EC,Della Pasqua O,Ploeger BA,Voskuyl RAdoi
10.1146/annurev.pharmtox.47.120505.105154subject
Has Abstractpub_date
2007-01-01 00:00:00pages
357-400eissn
0362-1642issn
1545-4304journal_volume
47pub_type
杂志文章,评审abstract::Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered inter...
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abstract::Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...
journal_title:Annual review of pharmacology and toxicology
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abstract::Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic...
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pub_type: 杂志文章,评审
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abstract::DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topo...
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更新日期:2013-01-01 00:00:00
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journal_title:Annual review of pharmacology and toxicology
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abstract::The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states--some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperex...
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更新日期:2015-01-01 00:00:00
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更新日期:2021-01-06 00:00:00
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更新日期:2000-01-01 00:00:00
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abstract::Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the int...
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abstract::Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a cova...
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更新日期:1995-01-01 00:00:00
abstract::Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and hav...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
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更新日期:2017-01-06 00:00:00
abstract::Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme ...
journal_title:Annual review of pharmacology and toxicology
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更新日期:2017-01-06 00:00:00
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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更新日期:2005-01-01 00:00:00
abstract::The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that ina...
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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abstract::The recent advances made in elucidating the processes of nociception have altered the way that chronic pain therapy and analgesic drug development are approached. Recent studies have highlighted new targets for drug discovery, including inhibition of inflammatory mediators (kinins, growth factors), newly expressed pro...
journal_title:Annual review of pharmacology and toxicology
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更新日期:1996-01-01 00:00:00
abstract::Imidazoline (I) receptors constitute a family of nonadrenergic high-affinity binding sites for clonidine, idazoxan, and allied drugs. One major subclass, the I1 receptors, whose subcellular distribution and signal transduction mechanisms are uncertain, partly mediates the central hypotensive actions of clonidine-like ...
journal_title:Annual review of pharmacology and toxicology
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更新日期:1996-01-01 00:00:00
abstract::Development of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab ov...
journal_title:Annual review of pharmacology and toxicology
pub_type: 历史文章,杂志文章
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更新日期:2017-01-06 00:00:00