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Functional mapping of drug response with pharmacodynamic-pharmacokinetic principles. 2010

Kwangmi Ahn, and Jiangtao Luo, and Arthur Berg, and David Keefe, and Rongling Wu
Center for Statistical Genetics, Pennsylvania State University, Hershey, PA 17033, USA.

Recent research in pharmacogenomics has inspired our hope to predict drug response by linking it with DNA information extracted from the human genome. However, many genetic models of drug response do not incorporate biochemical principles of host-drug interactions, limiting the effectiveness of the predictive models. We argue that functional mapping, a computational tool aimed at identifying genes and genetic networks that control dynamic traits, can help explain the detailed genetic architecture of drug response by incorporating pharmacokinetic and pharmacodynamic processes. Functional mapping is particularly powerful in determining the genetic commonality and differences of drug efficacy vs. drug toxicity and drug sensitivity vs. drug resistance. We pinpoint several future directions in which functional mapping can be coupled with systems biology to unravel the genetic and metabolic machinery of drug response.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010597 Pharmacogenetics A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION). Pharmacogenomics
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004364 Pharmaceutical Preparations Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069437 Pharmacological Phenomena Interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. Pharmacologic Processes,Pharmacological Processes,Pharmacologic Phenomena,Pharmacologic Phenomenon,Pharmacologic Process,Pharmacological Concepts,Pharmacological Phenomenon,Concept, Pharmacological,Concepts, Pharmacological,Pharmacological Concept,Phenomena, Pharmacologic,Phenomena, Pharmacological,Phenomenon, Pharmacologic,Phenomenon, Pharmacological,Process, Pharmacologic,Processes, Pharmacologic,Processes, Pharmacological
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D054316 Biomarkers, Pharmacological Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING). Biological Markers, Pharmacological,Drug Dosing Biomarker,Drug Dosing Biomarkers,Drug Response Biomarkers,Drug Safety Biomarkers,Biomarker, Drug Dosing,Biomarkers, Drug Dosing,Biomarkers, Drug Response,Biomarkers, Drug Safety,Dosing Biomarker, Drug,Dosing Biomarkers, Drug,Markers, Pharmacological Biological,Pharmacological Biological Markers,Pharmacological Biomarkers,Response Biomarkers, Drug,Safety Biomarkers, Drug
D019454 Chronotherapy The adaptation of therapeutic approaches such as pharmacological (DRUG CHRONOTHERAPY), surgical, radiological, or physical to the known variations in biological RHYTHMICITY, such as CIRCADIAN RHYTHMS. The treatment is aimed at supporting normal rhythms, or modifying the timing of therapy to achieve maximal efficacy and minimal adverse effect. Chronotherapies

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