bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems Biology: Applications in Drug Discovery
Authors: Ekins Sean , Bugrim Andrej , Nikolsky Yuri , Nikolskaya Tatiana 
Published: March 2010

AbstractSystem biology is the analysis of complex genes and proteins in an organism by integrating proteomic, genetic, metabonomic, and transcriptomic data through computational methods. It is rapidly becoming a leading approach to the integration and mining of data in human biology. This article discusses various utility, applications, and limitations of the tools and databases for such analysis.
Using Microsoft Excel® as a Laboratory Data Management Tool
Authors: Rubin A. Erik , Russo Mark F. , Neil William 
Published: March 2010

Abstract
Excel can be used by scientists for managing data management troubles ranging from simple tasks such as devising a system to store printouts of high‐performance liquid chromatography (HPLC) chromatograms and link them to entries in one's notebook to complicated scenarios such as creating a data storage and visualization application for a high‐throughput workflow that operates 24 h a day. There is an underappreciation for the wide diversity of data management tasks that can be handled by Excel and VBA. This article describes Excel's utility as a laboratory data management tool.
Design and Pharmaceutical Applications of Prodrugs
Authors: Järvinen Tomi , Rautio Jarkko , Masson Mar , Loftsson Thorsteinn 
Published: March 2010

AbstractProdrugs are pharmacologically inactive derivatives of drug molecules that require a chemical or enzymatic transformation in order to release the active parent drug in vivo, prior to exerting a pharmacological effect. Prodrug design aims to overcome limitations of a parent drug that would otherwise hinder its clinical use. Prodrug design and research should be more involved in the lead optimization step during the drug discovery process. This article focuses on the design and pharmaceutical applications of prodrugs.
Factors Influencing the Efficacy of Mediator‐Specific Anti‐Inflammatory, Glucocorticoid, and Anticoagulant Therapies for Sepsis
Authors: Minneci Peter C. , Deans Katherine J. , Haley Michael , Cui Xizhong , Natanson Charles , Eichacker Peter Q. 
Published: March 2010

AbstractSepsis is a major cause of mortality for hospitalized patients worldwide with a mortality rate estimated to be between 30 and 60 percent. It is observed that during sepsis, cardiovascular dysfunction is produced by bacterial infection with the release of bacterial toxins and the production of harmful host mediators. This article focuses on the rationale for targeting inflammatory and coagulant pathways during sepsis, reviews the clinical experience with mediator‐specific anti‐inflammatory agents, steroids, and anticoagulants, and highlights factors that growing evidence suggests may influence their efficacy.
Combinatorial Chemistry in the Drug Discovery Process
Authors: Ross Nathan T. , McNaughton Brian R. , Miller Benjamin L. 
Published: March 2010

Abstract
In recent years, combinatorial chemistry has evolved as an attempt to significantly shorten the lead identification and lead optimization portions of drug development. Combinatorial chemistry has become a widely used tool for synthetic chemists looking to streamline lead identification and for those needing novel structures to drive a plethora of studies in chemistry, biology, materials science, and beyond. This article describes the characteristics and applications of combinatorial chemistry in the drug discovery process.
Respiratory Viruses
Authors: Olivo Paul D. 
Published: March 2010

AbstractViruses cause cell death, organ malfunction, or elicit an inflammatory reaction that can account for many of the symptoms and pathology of infection. Respiratory viral infections have a major impact on health and cause an immense amount of human morbidity and mortality. This article focuses on the impact of respiratory viruses on health and therapeutic potential of antiviral therapy to control these agents.
Targets and Approaches for Cancer Drug Discovery
Authors: Mooberry Susan L. 
Published: March 2010

AbstractAlthough significant advances in early diagnosis and treatment of cancer have been made in the past decade, there remains a compelling need for more effective therapies for the treatment of many different types of cancer. Accurate predictive diagnostic tools are necessary to identify the molecular defects of tumors to allow for individualized targeted therapy. This chapter provides an introduction to the field of cancer drug discovery, focusing on a subset of current targets and giving a brief overview of approaches for identification of leads and sources of materials for drug discovery efforts.
Method Development for Preclinical Bioanalytical Support
Authors: Khan Masood , Weng Naidong 
Published: March 2010

AbstractPreclinical development represents a critical stage in the progression from discovery to marketed pharmaceutical drug candidates that have passed initial discovery screening and are identified to possess some drug‐like properties. Bioanalytical support at the preclinical development phase presents some unique challenges such as Good Laboratory Practice (GLP) and good metabolic selectivity coverage requirements. This article focuses on general bioanalytical method development, validation, sample analysis and practical experience on preclinical bioanalytical support.
Absorption of Drugs after Oral Administration
Authors: Granero Luis , Polache Ana 
Published: March 2010

AbstractAfter oral administration, drugs must be absorbed through the gastrointestinal tract to achieve the systemic circulation and exert their pharmacological effects. The successful formulation of an optimized oral drug delivery system requires a detailed consideration and a good understanding of the intestinal absorption process, its possibilities and limitations. This article gives an overview and update on the concepts, possibilities, and limitations of drug absorption after oral administration.
Distribution: Movement of Drugs through the Body
Authors: Panyam Jayanth , Patil Yogesh 
Published: March 2010

AbstractDrug distribution refers to the reversible movement of drug from blood to various tissues of the body. Following entry into the systemic circulation, a drug distributes into different tissues, the rate and extent of which is dependent on the drug's physicochemical properties and the blood flow to the tissues. This article focuses on the various factors affecting drug distribution and the different approaches available to modify drug distribution.
The Blood – Brain Barrier and its Effect on Absorption and Distribution
Authors: de Boer A. G. , Gaillard P. J. 
Published: March 2010

AbstractPotential drugs for the treatment of most brain diseases are often not able to cross barriers protecting the central nervous system (CNS). As a result, various drug delivery and targeting strategies are currently being developed to enhance the absorption and distribution of drugs into the brain. This article discusses the biology and physiology of the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier with respect to drug transport (absorption, distribution), the in vitro and in vivo methods to measure BBB transport, and the possibilities to deliver large molecular drugs, by viral and receptor‐mediated nonviral drug delivery, to the (human) brain.
Transporter Interactions in the ADME Pathway of Drugs
Authors: Zhang Yan , Miller Donald W. 
Published: March 2010

AbstractInteractions of therapeutic agents with endogenous transporter systems have a major impact on the absorption, distribution, metabolism, and excretion (ADME) properties of drugs. Pharmaceutical scientist has a variety of tools to probe transporter interactions of compounds. This article focuses on some of the important transporters that can influence the ADME properties of drugs and a strategy for evaluating compounds for transporter interactions.
Accumulation of Drugs in Tissues
Authors: Venkatesan Krishnamurthy , Bisht Deepa , Owais Mohammad 
Published: March 2010

AbstractDrugs need to achieve an adequate concentration in their target tissues in order to exert pharmacological action. The concentration of a drug at any moment and in any region of the body depends on translocation of the drug molecules and the chemical transformations they undergo due to metabolic action. This article focuses on movement of drug molecules across cell barriers, absorption, distribution, and various approaches for drug delivery.
Dissolution
Authors: Tiwary A.K. , Sapra Bharti , Jain Subheet 
Published: March 2010

AbstractDissolution of the active ingredients is of paramount importance for the successful performance of a dosage form. Dissolution testing is a convenient tool for ensuring intra‐ and interbatch performance compliance of dosage forms. This article focuses on factors influencing drug dissolution from dosage forms, dissolution test designing, and analysis of dissolution data
In VivoMetabolism in Preclinical Drug Development
Authors: Rollas Sevim 
Published: March 2010

AbstractIn preclinical drug discovery, investigation of the in vitro, in vivo metabolism and toxicity screening of a drug candidate together play a very important role in the drug's success before entering into clinical use. Several in vitro models, such as isolated perfused livers, liver tissue slices, freshly isolated hepatocytes in suspension, primary hepatocyte cultures, cell lines, microsomes, mitochondria, and expression systems have been developed to profile human metabolism. This article focuses on the preclinical in vivo metabolism of drug candidates and prodrugs.
Mechanisms and Consequences of Drug–Drug Interactions
Authors: Farkas Dora , Shader Richard I. , von Moltke Lisa L. , Greenblatt David J. 
Published: March 2010

AbstractUnderstanding the mechanisms and consequences of drug–drug interactions is essential for the development of new pharmaceuticals and for the design of multidrug regimens. Drug interactions occur when one drug changes the pharmacokinetic and/or the pharmacodynamic actions of another drug. This article focuses on the common mechanisms of drug–drug interactions and pharmacokinetic principles of drug interactions, including different experimental systems and modeling tools used to investigate possible drug interactions.
Species Comparison of Metabolism in Microsomes and Hepatocytes
Authors: Krebsfaenger Niels 
Published: March 2010

AbstractSpecies differences in metabolism may have significant impact on pharmacokinetics and toxicity of drugs. Therefore detailed knowledge of comparative metabolism across species is key for species selection in preclinical safety testing and interpretation of any animal data in respect to relevance for humans. This article focuses onin vitrospecies comparisons, which support a preliminary species selection for preclinical safety testing and interpretation of animal data.
Linkage Between Toxicology of Drugs and Metabolism
Authors: Zhang Ruiwen , Rayburn Elizabeth R. 
Published: March 2010

AbstractAlthough our ability to identify candidate lead compounds with high potency and specificity has largely been improved, many candidate therapeutic agents are prevented from reaching the market due to inappropriate pharmacokinetic/ADME properties and drug‐induced toxicity. As a consequence, over the past decades, ADME and toxicity (ADMET) screening studies have been incorporated earlier into the drug discovery phase for removal of poorly behaved drugs in the discovery and early development phases. This article focuses on fundamental ADMET concepts, key tools, reagents, and experimental approaches for predicting human pharmacokinetics and assessing “drug‐like” molecules, with an emphasis on the link between toxicology and metabolism.
Experimental Design Considerations in Pharmacokinetic Studies
Authors: Hope William W. , Petraitis Vidmantas , Walsh Thomas J. 
Published: March 2010

Abstract
Pharmacokinetic studies are conducted in experimental contexts to define pharmacokinetic relationships for new drugs that may be beneficial for patients and to enable the understanding the concentration‐effect relationships. For both these purposes, an accurate description of pharmacokinetics is vital, which can be achieved by appropriate experimental design. This article describes some of the issues in the design of experimental models, which enable pharmacokinetic relationships to be established.
Pharmacodynamics
Authors: Shin Beom Soo , Shah Dhaval , Balthasar Joseph P. 
Published: March 2010

AbstractPharmacodynamics refers to the study of relationships between drug concentrations and pharmacological effects. The mathematical description of these relationships, through the use of appropriate pharmacodynamic models, facilitates the characterization and comparison of candidate drugs, facilitates the rational selection of appropriate dosing regimens, and assists in the investigation and identification of the mechanisms associated with drug action. This article provides an overview and a catalog of mathematical models that may be employed to characterize drug pharmacodynamics.
Regulatory Requirements forINDs/FIH(First in Human) Studies
Authors: Gad Shayne Cox 
Published: March 2010

AbstractThe safety of pharmaceutical agents, medical devices, and food additives is the toxicology issue of the most concern to the public. Chapter 1, Title 21 of theCode of Federal Regulations(21 CFR) govern the testing, manufacture, and sale of pharmaceutical agents in the U.S. This article examines the regulations that establish how the safety of human pharmaceutical products is evaluated and established in the United States and the other major international markets prior to initial trials in human beings.
Use of Project Teams in Preclinical Development
Authors: Keefe Dorothy M. K. , Bowen Joanne M. , Gibson Rachel J. 
Published: March 2010

AbstractPreclinical development of a drug is that part of drug development that occurs before the drug enters human trials. The process includesin vitroandin vivostudies of efficacy, safety, pharmacokinetics, and pharmacodynamics, in order to produce pharmaceutical grade materials. This article highlights the role and use of project teams in preclinical development.
Repeat Dose Toxicity Studies
Authors: Gad Shayne Cox 
Published: March 2010

Abstract
Repeat dose toxicity studies are those studies whereby animals have a therapeutic agent administered to them on a regular and repeated basis by one or more routes. Repeat dose study is a broad exploration of the cumulative biological effects of the administered agent over a range of doses. This article focuses on various objectives for repeat dose studies, the regulatory requirements governing them, and the key factors in their design and conduct.
Safety Assessment Studies: Immunotoxicity
Authors: Descotes Jacques 
Published: March 2010

AbstractThe clinical shift from immunology to toxicology resulted in the introduction of toxicological concepts in immunotoxicity evaluation. Current procedures for assessing the immunotoxicological safety of medicinal products have some shortcomings. Nonclinical immunotoxicity evaluation is currently limited to unintended immunosuppression. This article discusses various safety factors related to immunotoxicity, including preclinical assessment of immunosuppression and models of IgE mediated hypersensitivity reactions.
Toxicologic Pathology
Authors: Tchounwou Paul B. , Centeno José A. 
Published: March 2010

Abstract
The science of toxicologic pathology has been critical for the understanding of adverse effects of physical, chemical, and biologic agents on biologic systems. Toxicologic pathology has emerged as a scientific discipline that integrates toxicology and pathology. This article discusses important aspects of toxicologic pathology at the molecular and cellular levels and also presents an overview of radiation‐induced toxicologic pathology.
Preclinical Development of Protein Pharmaceuticals: An overview
Authors: Das Dipankar , Suresh Mavanur R. 
Published: March 2010

AbstractBiogeneric protein pharmaceuticals are a new category of therapeutics. Almost all of the current approved biopharmaceuticals are therapeutic proteins and vaccines. This article presents an overview of various aspects of preclinical development of protein pharmaceuticals, including influence of carbohydrate in protein drugs and immunogenicity issues.
Auditing and Inspecting Preclinical Research and Compliance with Good Laboratory Practice (
GLP
)
Authors: Dent N.J. 
Published: March 2010

Abstract
The Good Laboratory Practice (GLP) guidelines have progressed through various transitional phases to become guidelines in some countries and regulatory/statutory instruments in others. The objective of the GLPs is to ensure that a standard approach is undertaken, covering traceability and accountability of medical research and drug development process. This article discusses various aspects of auditing and inspecting preclinical research compliance with GLP.
Biotransformations in Drug Metabolism
Authors: King Roberta S. 
Published: March 2010

AbstractMetabolism can affect the spectrum of consequences of drug action including both the desired therapeutic effects and undesired effects. During the clinical studies and post‐marketing stages, metabolism data can be used to promote safe use of a drug, including dosing adjustments or warnings about drug‐drug interactions. This article discusses various stages of biotransformations in drug metabolism including functional group biotransformation and major P450 reactions.
Pharmacogenetics and Pharmacogenomics
Authors: Yengi Lilian G. 
Published: March 2010

AbstractThe fields of pharmacogenetics, genomics, and drug transporters have profoundly impacted drug metabolism research by providing plausible mechanisms for interindividual variability in drug response and metabolism‐related toxicity. Pharmacogenetics is a branch of study that analyzes the effects of genetic differences between individuals. This article discusses various issues related to pharmacogenetics, including gene regulation and its potential impact on the efficacy and safety of new drug candidates.
Introduction to Drug Transporters
Authors: Leung Louis , Oganesian Aram 
Published: March 2010

AbstractThe role of transporter proteins in drug and endogenous substance disposition has increasingly gained recognition over the last decade. Inhibition or induction of different drug transporters in different tissues can lead to clinical drug‐drug interactions that may result in adverse effects or lack of efficacy. The article offers insights into the role of drug transporters in drug development, drug absorption, metabolism, and toxicity.
Approaches to Performing Metabolite Elucidation: One Key to Success in Drug Discovery and Development
Authors: Nassar Ala F. 
Published: March 2010

AbstractAbsorption, distribution, metabolism, excretion, and toxicology (ADMET) studies are widely used in drug discovery and development. Drug discovery efforts have been aimed at identifying and addressing drug metabolism issues at the earliest possible stage. Metabolite identification is crucial to the drug discovery and development process. The article discusses approaches to performing metabolite elucidation at various drug development stages.
An Introduction to Metabolic Reaction Phenotyping
Authors: Davis Carl D. , Rodrigues A. David 
Published: March 2010

AbstractOptimizing the metabolic stability of a new chemotype in drug discovery can improve oral bioavailability and help to identify a drug candidate that will achieve efficacious exposure in the target patient population. The role of drug‐metabolizing enzymes (DMEs) and metabolic clearance in the overall determination of a drug's oral bioavailability and pharmacokinetics (PK) is fully incorporated into the process of discovery and development of improved therapeutic agents. This article describes experimental and kinetic methods used to identify the role of enzymes in the overall metabolic clearance of a drug and illustrates some concerns related to the contribution and interindividual variation of some notable enzymes.
Pharmaceutical Excipients in Drug–Drug Interaction
Authors: Chen Chuan , Sadeque Abu J.M. 
Published: March 2010

AbstractDuring the development of a given drug formulation, the interactions between the drug and excipients need to be carefully studied to ensure that the drug is stable in the formulation. Enzyme‐based drug interaction involving excipients appears to occur predominantly in preclinical studies. The article discusses drug‐drug interaction potential of pharmaceutical excipients, with a focus on solubilizing excipients.
Role of Bioactivation Reactions in Chemically Induced Nephrotoxicity
Authors: Lash Lawrence H. 
Published: March 2010

AbstractKidneys express a diverse array of enzymes that can catalyze the bioactivation of many drugs and xenobiotics. The kidneys are particularly susceptible to chemically induced toxicity because of their basic physiology and biochemistry. The article discusses the role of bioactive reactions in chemically induced nephrotoxicity.
Demonstration of Comparability of a Licensed Product after a Manufacturing Change
Authors: Lewis Richard M. 
Published: March 2010

AbstractThe demonstration of comparability of a licensed product after a manufacturing change has been addressed by several published regulatory guidance documents, such as the FDA guidance, the EMEA guideline, and the ICH guidance. The comparability exercise may include a combination of analytical testing, biological assays, assessment of pharmacokinetics and/or pharmacodynamics and toxicity in animals, and clinical testing. This article focuses on the regulatory guidelines and general principles and practices for determining comparability of a licensed product after a manufacturing change.
Enzyme Replacement Therapies
Authors: Andrews Laura , O'Callaghan Michael 
Published: March 2010

Abstract
Enzyme replacement therapy (ERT) is a therapeutic approach where the specific enzyme that is absent or inactive in affected individuals is replaced with a functional enzyme molecule. Significant advances in enzyme replacement therapy that has opened up a new era of hope for lysosmal storage disease (LSD) sufferers. This article addresses the issues facing development of enzyme replacement treatments for lysosmal storage diseases (LSDs).
Toxicology of Oligonucleotide Therapeutics and Understanding the Relevance of the Toxicities
Authors: Levin Arthur A. , Henry Scott P. 
Published: March 2010

AbstractThere are four categories of oligonucleotide therapeutics. These include the following: single‐stranded oligonucleotides that work through RNAse H or steric effects; double‐stranded RNAs that work through the dicer pathway; immunostimulatory oligonucleotides that work by stimulating innate immunity, and aptamers that work by binding to proteins and modifying their function. This article describes the existing practices for assessing the toxicity of oligonucleotide therapeutics and the rationale for these practices.
Preclinical Safety Evaluation of Monoclonal Antibodies
Authors: Treacy George , Martin Pauline 
Published: March 2010

Abstract
Monoclonal antibodies are populations of identical, monospecific antibodies with defined specificity and affinity for a target antigen. The design of preclinical safety evaluation of monoclonal antibodies is based on the class of monoclonal, the target epitope, and the clinical indication. This article focuses on preclinical safety evaluation of monoclonal antibodies.