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Pharmacogenomics  & Personalized Medicine glossary & taxonomy
Evolving Terminologies for Emerging Technologies
Comments? Questions? Revisions? Mary Chitty 
mchitty@healthtech.com
Last revised November 14, 2013
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Pharmacogenomics is often referred to as a "revolution" or "the great new wave" in medicine - a future filled with promise not just for better, safer, and ore affordable healthcare (i.e. affordable for both consumers and third-party payers) but also, according to some, greater economic returns for drug makers. While there are in fact a handful of drugs on the market with genotype-based prescribing requirements, such as Herceptin, this next great wave has been slow to arrive. Insight Pharma Reports, Pharmacogenomics: Delivering on the promise, 2009 

Guide to terms in these glossaries    Site Map  Related glossaries include Diagnostics  Biomarkers    Molecular diagnostics, genetic & genomic testing 
Clinical   Cancer diagnostics, genomics, prognostics & therapeutics    Drugs  Drug safety & pharmacovigilance  Drug targets
Informatics: Drug discovery informatics  Clinical & medical informatics   Technologies  Metabolic engineering & profiling   Microarrays   Sequencing
Biology Expression, gene & protein  Genomics
   SNPs & genetic variations

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ADME: Abbreviation for Absorption, Distribution, Metabolism, Excretion. See also pharmacokinetics, drug disposition. [IUPAC Med Chem] Also referred to as ADME/ Tox ADME/ Toxicology or ADMET

These key properties of pharmaceutical compounds are tested for as part of lead optimization activities. Related terms: DMPK, pharmacokinetics, predictive ADME, toxicogenomics.

chronopharmacokinetics: Pharmacokinetic parameters are generally assumed to be invariate with the time of day, although circadian variation of drug metabolism and drug response is known. As proposed, chronopharmacokinetics considers the implications of the chronovariability of pharmacokinetic parameters. In order to investigate chronovariation in the rate of disappearance of a substance from the approximate a linear course until very low blood levels are attained. ... It is concluded that: 1) rhythmicity within elimination curves can only be determined by repetition of the experiment at different times of the diel period; 2)the expectation that a rate-constant estimated at one time of the day may be valid for another part of the day carries with it an unknown risk. No pharmacokinetic analysis can be considered definitive unless chronopharmacokinetic variation of parameters is considered. FM Sturtevant, Chronopharmacokinetics of ethanol. I. Review of the literature and theoretical considerations, Chronobiologia 3(3): 237- 262, Jul-Sept 1976  

chronopharmacology:  The science dealing with the phenomenon of rhythmicity in living organisms is called chronobiology. The branch dealing with the pharmacologic aspects of chronobiology is termed chronopharmacology, which may be subdivided into chronotherapy, chronopharmacokinetics and chronotoxicity. WA Ritschel, H Forusz, Chronopharmacology: a review of drugs studied, Methods Find Exp Clin Pharmacology 16(1): 57- 75, Jan-Feb 1994    Related terms; Pharmacogenomics

clinical pharmacology:   The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. MeSH, 1980

Over the past decades, the scope of clinical pharmacology within the pharmaceutical industry has widened considerably. Key growth has been in the area of translational science and exploratory medicine, where clinical pharmacologists are nowadays the mediator between basic research and establishment of clinical usefulness. This role has led to and is supported by the rapid developments in pharmacokinetic-pharmacodynamic modeling and simulation, a strong focus on biomarkers for early informed decision-making, and the advent of pharmacogenomics into safety and efficacy predictions and evaluations. The ultimate goal - safer, more efficacious drug prescription - is shared with that of today's drive for more personalized medicine. This article reviews the evolution of clinical pharmacology within the industry, the regulatory, clinical and societal drivers for this evolution, and the analogy with the establishment of personalized medicine in clinical practice. Clinical pharmacology, biomarkers and personalized medicine: education please. Koning P, Keirns J. Biomark Med. 2009 Dec;3(6):685-700. http://www.ncbi.nlm.nih.gov/pubmed/20477707

clinical pharmacometabolomics:  The segregation of patient populations using small molecule biomarkers in clinical trials, adverse drug reaction, and drug efficacy evaluation.  Phenomenome Discoveries http://www.phenomenome.com/  Broader term: pharmacometabolomics

computational pharmacology: Our ultimate goal is transforming the process of drug design through the use of advanced computational techniques, particularly machine learning and knowledge- based approaches applied to high throughput molecular biology data. We create novel algorithms for the analysis and interpretation of gene expression arrays, proteomics, metabonomics, and combinatorial chemistry. We also create tools for building, maintaining and applying knowledge- bases of molecular biology, and for knowledge- driven inference from multiple biological data types. Finally, we are developing and applying natural language processing techniques for information extraction from and management of the biomedical literature. The UCHSC Center for Computational Pharmacology, Univ. of Colorado Health Sciences Center, US http://compbio.ucdenver.edu/Hunter_lab/ 

computational therapeutics: Molecular Medicine
computational toxicology: Drug safety & pharmacovigilance 

cytochrome P450 enzymes: The most important and well- studied group of drug- metabolizing enzymes, the cytochrome P450 enzymes (found in the liver) are responsible for the metabolism of a large number of pharmaceutical compounds. These enzymes function to detoxify xenobiotics (foreign molecules in the body, including drugs). The various genetic polymorphisms in cytochrome P450 can result in increased enzymatic activity, decreased enzymatic activity, or complete loss of enzyme activity. These changes can, in turn, lead to increased (or decreased) activation of pro- drugs, or to increased (or decreased) metabolism and excretion of drugs. 

DMPK: Drug metabolism and pharmacokinetics.   Related terms: ADME

disease resistant individuals: Another interesting group [of phenotypes for pharmacogenomics] includes those who have no disease yet have high risk factors.  A classic example are individuals who exposed themselves to multiple risk factors for HIV - unprotected intercourse with multiple partners, intravenous drug use, etc. - and who either did not get the disease, or when they did get it, it progressed very slowly. Interestingly, a gene target was identified in this group - the CCRX deletions.  There are many other disease- resistant groups in medicine. ... In general, disease- resistant groups provide a way of identifying given targets that are pre- validated in human subjects.

drug metabolism: About 150 terms directly related to the field of drug metabolism will be compiled and defined by this expert group for dissemination to the scientific community. This will help achieve a common definition base across the various publications in this field. … The working party has pared-down its initial, all- inclusive list of over 600 terms related to drug metabolism, to a focused list of about 170 terms. The latter better represents just those terms that are the most relevant for medicinal chemistry. IUPAC Metabolism terms, project Number: 2000-009-1-700, 2002 http://www.iupac.org/projects/2000/2000-009-1-700.html

Drug Metabolizing Enzymes DME genes: The biochemical and transcriptional mechanisms by which drugs and xenobiotics affect the expression of the Phase I (cytochrome P450) and Phase II (e.g, glutathione S-transferase) drug metabolizing enzymes (DMEs). These important proteins are responsible for metabolizing endogenous compounds such as steroids, prostaglandins, and leukotrienes, as well as drugs and environmental pollutants. A notable characteristic of some DME genes is their ability to be transcriptionally upregulated by treatment with chemical  inducers such as phenobarbital (PB). [Jeff DeJong, Biology Dept. Univ. of Texas at Dallas]  http://nsm1.utdallas.edu/bio/Dejong/dej99.html

drug response: Includes drug dispositions (pharmacokinetics, PK) and drug effect (pharmacodynamics, PD). E15 terminology in Pharmacogenomics, ICH,  2008 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129296.pdf 

Comparison of pharmacogenomics studies will be difficult until a more standard definition of "response" and of various phenotypes can be agreed upon. 

drug response phenotype: SNPs are also useful in pharmacogenomics for matching an individual’s genotype with a drug- response phenotype. It is possible, in this context, to identify individuals who cannot adequately metabolize the drug and must be dosed accordingly, or those with a compromised drug target, who could not benefit from the drug. The discovery of such a relationship will require measuring hundreds of SNPs in or near candidate genes in several thousands of individuals. Validation will require detecting very few SNPs in several hundred to several thousand individuals. These relationships can be used either for clinical trials or diagnostically to determine therapy. Each clinical trial will involve measuring few SNPs in the low thousands of individuals.

enzyme kinetics:  Most of the chemical reactions which occur in living systems, if left to their own devices, would occur at rates which are very slow, some immeasurably slow. Catalysts are required to make these reactions go at rates that are useful to the cell. In biological systems the catalysts are enzymes. [Introduction, Enzyme Kinetics Tutorial, Biochemistry & Molecular Biology Dept., Thomas Jefferson Univ., US] http://jeffline.tju.edu/CWIS/DEPT/biochemistry/kinetics/HTML/PAGE1.HTMLexpression pharmacogenomics:  Applies genome/proteome scale differential expression technologies to both in vivo and in vitro models of drug response to identify candidate markers correlative with and predictive of drug toxicity and efficacy. It is anticipated to streamline drug development by triaging towards lead compounds and clinical candidates that maximize efficacy while minimizing safety risks. Bonnie E. Gould Rothberg "Use of animal models in expression pharmacogenomic analysis" (Pharmacogenomics Journal 1: 48-58, 2001 http://www.nature.com/tpj/journal/v1/n1/abs/6500008a.html  Related terms: Expression, genes & more

FDA guidelines: Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

flip flop pharmacokinetics:  a phenomenon often encountered with extravascularly administered drugs…. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters.  Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development. Yanez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM Ther Deliv 2011 May;2(5):643-72.  http://www.ncbi.nlm.nih.gov/pubmed/21837267 Broader term: pharmacokinetics

genomic data: PGx [pharmacogenomics] and PGt [pharmacogenetics] research depends on the use of samples to generate data. A harmonised definition for the coding of these samples and their associated data will facilitate use in research and development of new medicines. E15 terminology in Pharmacogenomics, ICH, 2008 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129296.pdf 

genomic data samples coding: There are four general categories of coding: identified, coded, anonymised and anonymous. Coded data or samples can be single or double coded. The implications of using a specific data and sample coding category should be considered in the design of PGx [pharmacogenomics] and PGt [pharmacogenetic] research studies. E15 terminology in Pharmacogenomics, ICH, 2008 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129296.pdf  

genotype-to-phenotype:  Investigators start with a set of genes that are known (or strongly suspected) to be important in modulating the response to drugs, and search for variation in their sequences (that is, their genotype.) Given an understanding of genetic variations, they then search for the phenotype consequences.  Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, c.2001 http://bmir.stanford.edu/file_asset/index.php/91/BMIR-2001-0898.pdf  Compare phenotype-to-genotype

Gleevec Cancer genomics
Herceptin
Cancer genomics

idiosyncratic toxicity: Few drug development surprises can be as devastating as toxicity problems that only show up under a combination of conditions as idiosyncratic toxicity. Because of the role of variations in human drug metabolizing enzymes there may only be subtle (or no) evidence of such problems during pre-clinical safety studies. Such problems are also unlikely to show up in all but the largest clinical trials, but if the side effects are serious, it can result in product withdrawal.   Idiosyncratic toxicity: Understanding, Prediction and Prevention, Nov. 17-18, 2004, Philadelphia PA

immunophenotyping: The recording of observable immunological characteristics of an individual, which result from interaction between the genes of that individual and the environment. [NASA's Neurolab glossary, 1997] http://neurolab.jsc.nasa.gov/glossim.htm   Wikipedia http://en.wikipedia.org/wiki/Immunophenotyping 

in silico pharmacology:  Bioinformatics is used in drug target identification and validation and in the development of biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic benefit of drugs. Now that the 'parts list' of cellular signalling pathways is available, integrated computational and experimental programmes are being developed, with the goal of enabling in silico pharmacology by linking the genome, transcriptome and proteome to cellular pathophysiology. PA Whittaker, What is the relevance of bioinformatics to pharmacology? Trends in Pharmacological Sciences. 24 (8): 434- 439, August 2003.   See also under computational pharmacology

in vivo pharmacology: To understand fully the role of a gene in health and disease, it is necessary to know how it contributes to the complex physiology of the organism. There are several emerging biotechnologies of highly significant scientific and medical value, which require in vivo skills. The best established of these is the knockout animal in which a gene encoding an enzyme, mediator, neurotransmitter or receptor has been selectively disrupted. The generation of the disrupted gene and its introduction into the animal genome are achieved by molecular biologists. Once successful, gene disruption has consequences that require the attention of in vivo biologists. The combination of molecular biology and integrated biology provides a very powerful analytical tool with which to investigate disease. Other such combinations are provided by techniques, including: (1) conditional gene knockout and knock-in techniques, which allow the expression of genes to be up- or downregulated at any time; (2) the use of cell specific promoters to regulate the expression of genes in selected cells [19]; (3) transgenic expression of human genes; and (4) expression in animals of mutated genes that have been identified as possible mediators of disease in humans  In each case, the skills in molecular manipulations have to be combined with skills of in vivo investigations to realize the full (and sometimes completely unexpected [21]) effects of the molecular changes.  [in vivo Pharmacology Training Group, Fall and Rise of in vivo Pharmacology, HMS Beagle, Issue 120, Feb. 15- 28, 2002] http://news.bmn.com/hmsbeagle/current/notes/feature3

individualized medicine: Another term for pharmacogenomics.  One key issue for pharmacogenomics is just how individualized drug therapies are going to become.  There is fundamental tension between the economics of faster and cheaper medical care and customized prescriptions and therapies.  Haplotypes offer hope, as does the tradeoffs between liability for patients likely to encounter adverse events who can be screened out before they take a drug and the prospect of overly fragmented pharmaceutical segments.   Related term: personalized medicine

influence-based data mining: See Algorithms & data management  for relevance of this technique to pharmacogenomics data.

kinetic outliers: Intersubject variability - in particular, the presence of kinetic outliers - is encountered during the course of a drug development program. Often, these outliers can be explained by genetic variability or polymorphism in cytochrome CYP450 genes responsible for drug metabolism. Genetic analysis of outliers could help explain the variability in metabolism and possibly influence the development and labeling of the drug in question.  Related term: pharmacokinetics

LD 50:  The dose of a substance that will kill half (50%) of the treated test animals when given as a single dose.  A measure of acute toxicity. [Chemical Hygiene Glossary of Terms, Environment, Health & Safety Lab, Lawrence Berkeley National Laboratory, US]

mechanism of action: For many, if not most, of the drugs on the market today, we have limited information about the compound’s mechanism of action. Yet, understanding a compound or biologic’s mechanism of action enables companies to improve a drug’s selectivity and potency and reduce the high attrition rates associated with adverse “Off-Target Effects” in a drug or biologic’s development. Through mechanism of action studies we can determine how a compound or biologic binds to and changes the physiologic state of its given target or pathway and identify adverse “Off-Target Effects” that arise when that compound or biologic binds to a non-intended target. This enables companies to drive substantial value in their drug discovery and development pipelines and enables Medicinal Chemists to rationally design improved 2nd and subsequent generations of compounds in development to improve their efficacy and safety. Mechanism of Action: Driving Pipeline Value through Understanding Compounds, Targets and Interactions Oct 2009 Boston MA   Order CD

A more detailed, molecular description of events. Genetic Toxicology Association, Spring 2000 meeting  report  

The knowledge of mechanisms of action is important for two reasons: (1) you need secondary assays that are really associated with a mechanism of action in order to optimize leads in the best possible way, and (2) the FDA will increasingly require that you know the mechanism of action, before you go into clinical trials, to prevent possible toxic side effects. ... The good news is that an increasingly large percentage of drugs that are going through the pipeline now have known mechanisms of action (MOAs) at a molecular level, which is a contrast to 10 to 20 years ago. We now are understanding how therapies interact with the human body and with disease on a much more detailed level. Most drugs now have known targets, and most targets participate in known pathways. The caveat to that, as I mentioned earlier, is that biology is very complicated, and we’re learning that the target isn’t enough. It’s not enough to simply know that a certain molecule binds to a certain protein and turns it off. What you really need to know about are the pathways, and the side pathways, and the domains, and the homologous targets.  Broader term: mode of action  Narrower term: molecular mechanism of action

median effective dose: The dose of a drug predicted (by statistical techniques) to produce a characteristic effect in 50 percent of the subjects to whom the dose is given. The median effective dose (usually abbreviated ED50) is found by interpolation from a dose- effect curve. The ED50 is the most frequently used standardized dose by means of which the potencies of drugs are compared. Although one can determine the dose of drug predicted to be effective in one percent (ED1) or 99 percent (ED99) of a population, the ED50 can be determined more precisely than other similar values. An ED50 can be determined only from data involving all or none (quantal) response; for quantal response data, values for ED0 and ED100 cannot be determined. In analogy to the median effective dose, the pharmacologist speaks of a median lethal dose (LD50), a median anesthetic dose(AD50), a median convulsive dose (CD50), etc. [Edward W. Pelikan, Glossary of terms and symbols used in pharmacology, Boston University Medical School, US, 1993- 1998

metabolism- medicinal chemistry: Pharmaceutical biology  See also drug metabolism

metabonomics/metabolomics: In the context of toxicology, this approach involves evaluating tissues and biological fluids for changes in metabolite levels that result from toxicant exposure. In one early manifestation, proton nuclear magnetic resonance (NMR) studies can produce signal patterns representing metabolite mixtures; these patterns can be correlated with toxicant mechanism or identity of affected organs. CHI report Toxicogenomics: The Promise of Safer, Smarter Drug Development,  2002  See also -Omes & -omics  metabolomics, metabonomics

mode of action MOA: Examples of MOAs that are usually encountered include mutagenicity, mitogenesis, inhibition of cell death, immune suppression, among others. [Genetic Toxicology Association, Spring 2000 meeting report] http://www.ems-us.org/gta/springr00.html

The process governing the action of chemicals without the level of detail required to determine mechanism of action

molecular mechanisms of action: Activities at the molecular level of exogenous compounds affecting normal biochemical pathways, including the actions of PROTEINS; CELL SURFACE RECEPTORS; NEUROTRANSMITTERS; and inhibitors.  MeSH 2004  See also mechanism of action

molecular pharmacology: Knowledge about drugs interacting with known target molecules and the identification of novel target molecules. . Molecular and Systems Pharmacology, Emory University, 2006 http://biomed.emory.edu/programs/program_msp.cfm  Related term: systems pharmacology

molecular phenotyping: Epidemiologists, clinical trialists and experimental scientists are confronted with a wealth of potential ‘omic’ technologies for the ‘molecular phenotyping’ of large numbers of biological samples obtained from cohorts, patients or animal models.  The challenge now is to use these technologies effectively to define the relationships between sets of biomarkers and disease.  The concept of the MolPAGE project is to bring together a scientific consortium with the necessary expertise to enable the development of these ‘omic’ technology tools to permit high-throughput analyses of significant numbers of samples, to ensure that protocols are established for sample collection and storage, and that systems are in place to capture, warehouse, analyse and integrate the range of biological data that will emerge from these studies.  MolPAGE Molecular Phenotyping to Accelerate Genomic Epidemiology European Union FP6 2007 http://www.molpage.org/index.asp 

network pharmacology: The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy... However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.  Network pharmacology: the next paradigm in drug discovery, AL Hopkins, Nature Chemical Biology 2008 Nov; 4(11): 682- 690.   

oncopharmacogenomics: Identifying targets for anti- cancer drugs based on genomic vulnerability. GRA Georgia Research Alliance Annual Report, 2001  Related terms:  BiomarkersCancer genomics

organ systems pharmacology: See integrative and organ systems pharmacology

personalized medicine: Remarkable advances in the field of pharmacogenomics—how individuals react differently to medicines—indicate that we are moving away from “one-size-fits-all” medicine. Scientists can now identify glitches in our DNA scripts that reveal what drugs may be dangerous—or completely ineffective—for certain people. This information will help doctors calculate precise dosages that match a person’s DNA. … Already, pharmacogenomic information is contained in about 10% of labels for drugs approved by the FDA to treat a range of conditions including HIV/AIDS, cancer, seizures, and cardiovascular disorders. NIH Personalized Medicine 2011 http://www.nih.gov/about/discovery/technology/personalmed.htm

The first example of personalized medicine is the HIV test, but instead of genotyping the host, this test involves genotyping the virus and determining what drugs are most effective against the virus or which drugs the virus shows the least resistance to. Pharmacogenetics Offers New Opportunities in Disease Treatment and How Medicines Are Marketed: An Interview with Craig Fitzgerald of HealthCarta, CHI's GenomeLink 25.2 http://www.chidb.com/newsarticles/issue25_2.asp 

Priorities for Personalized Medicine, President's Council of Advisors on Science and Technology Policy,  2008 http://www.ostp.gov/galleries/PCAST/pcast_report_v2.pdf   .  Related terms: individualized medicine, pharmacogenomics

Pgx:  Collective use of pharmacogenetics and pharmacogenomics. NIH comments on FDA's draft guidance for Industry Pharmacogenomic Data Submission, Docket No. 2003D-0497, Feb. 2004 http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03D-0497_emc-000009-01.pdf  

pharmacodynamics: Study of the biochemical and physiological processes determining the effects of drugs on organisms. Narrower terms: pharmacokinetics;  pharmacodynamic biomarkers  Related terms: ADME, mechanism of action, mode of action

pharmacoepigenomics: MGMT hypermethylation demonstrates the possibility of pharmacoepigenomics: methylated tumors are more sensitive to the killing effects of alkylating drugs used in chemotherapy. M Esteller, JG Herman, Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer, Oncogene 23(1): 1-8, Jan 8, 2004 

This review argues that the epigenome, which plays a critical role in controlling gene expression, plays also an important role in drug responsiveness. The epigenome is composed of chromatin and its modifications and DNA methylation. DNA methylation and chromatin structure are dynamic and tightly linked. Alterations in DNA methylation are involved in the pathology of cancer and in normal aging. It is suggested here that pharmacoepigenomics should be recognized as a new field in pharmacology. This field will address the epigenomic basis of issues which were traditionally the focus of pharmacogenetics and pharmacogenomics such as inter-individual differences in drug responsiveness, the impact of drugs on gene expression profiles, identification of unpredicted side effects of drugs at early stages of preclinical development and the discovery of novel drug targets. Moshe Szyf, Toward a Discipline of Pharmacoepigenomics, Current Pharmacogenomics, 2 (4): 357- 377, Dec. 2004 http://www.ingentaconnect.com/content/ben/cpg/2004/00000002/00000004/art00006  

Epigenomics, official journal of the DNA Methylation Society, Moshe Szyf, editor http://www.landesbioscience.com/journals/epigenetics/callforpapers.php

pharmacogenetic test: An assay intended to study interindividual variations in DNA sequence related to drug absorption and disposition (pharmacokinetics) or drug action (pharmacodynamics) including polymorphic variation in the genes that encode the functions of transporters, metabolizing enzymes, receptors, and other proteins. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

Pharmacogenetic tests and genetic tests for inheritable markers: Guidance for Industry and FDA Staff, CDER,  FDA, 2007 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm077862.htm 

pharmacogenetics: A subset of pharmacogenomics and is defined as The influence of variations in DNA sequence on drug response. ... does not include other disciplines such as proteomics and metabonomics.  E15 terminology in Pharmacogenomics, ICH, 2008 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129296.pdf 

The terms "pharmacogenomics" and "pharmacogenetics" are often interchanged and used without clear definition. For the purpose of this meeting, I will use working definitions. Pharmacogenetics refers to people including gene identification and "right medicine for right patient." Pharmacogenomics refers to the application of tools including, but not limited to, the functional genomics toolbox of differential gene expression (DGE), proteomics, yeast 2- hybrid (Y2H) analyses, tissue immuno- and histopathology, etc. There are two applications of pharmacogenetics that may use similar techniques but are quite distinct: a) susceptibility gene identification and b) "right medicine for right patient" . Allen D. Roses "Pharmacogenetics and pharmacogenomics in the discovery and development of medicines " Pharmacogenetique et Pharmacogenetique, Institut Pasteur, Paris [France], 12-13 Octobre 2000, Institut Pasteur  http://www.pasteur.fr/applications/euroconf/pharmaco/pharmaco-prog.html

A subset of pharmacogenomics encompassing the study of genetic variation underlying differential response to drugs, particularly genes involved in drug metabolism. 

With the implementation of pharmacogenetics, diseases will be evaluated by mechanisms, rather than just symptoms, and early response will be based on prognosis and susceptibility rather than just diagnosis. It will introduce a bottom- up approach to disease, which will be defined in terms of its heterogeneity, and not "averaged out" to conform to a uniform model.    See also pharmacogenomics

pharmacogenetics- drug development: You want to use that [pharmaco] genetic knowledge to screen for efficacy or safety so that instead of enrolling 2- 3,000 patients you might only have to enroll 500 or 600. That could limit your costs significantly. When you have to recruit 500 versus thousands, the development costs are much lower. Being able to use a diagnostic that will predict adverse events could be significant; if you just look over the last ten years at the number of drugs removed from the market due to ADRs in a small segment of the population, giving the FDA and the industry alternatives could save billions of dollars in improved care. Pharmacogenetics Offers New Opportunities in Disease Treatment and How Medicines Are Marketed: An Interview with Craig Fitzgerald of HealthCarta, CHI's GenomeLink 25.2 http://www.chidb.com/newsarticles/issue25_2.asp 

pharmacogenetics - drug discovery: I think that pharmacogenetics has already arrived for drug discovery. A cytochrome P450 test is available, and a lot of companies are setting up screening for metabolic pathways as part of drug discovery. That approach can save companies a lot of time and energy; they can engineer molecules that should not have that drug interaction and metabolism problem. Pharmacogenetics Offers New Opportunities in Disease Treatment and How Medicines Are Marketed: An Interview with Craig Fitzgerald of HealthCarta, CHI's GenomeLink 25.2  http://www.chidb.com/newsarticles/issue25_2.asp 

pharmacogenome: -Omes & -omics

pharmacogenomic test: An assay intended to study interindividual variations in whole genome or candidate gene, single nucleotide polymorphism SNP maps, haplotype markers, or alterations in gene expression or inactivation that may be correlated with pharmacological function and therapeutic response, In some cases the pattern or profile of change is the relevant biomarker, rather than changes in individual markers.  Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

pharmacogenomics: Despite their slightly different definitions, as with other "-genetics" and "-genomics" terms, pharmacogenomics (PGt) and pharmacogenomics (PGx) are often used interchangeably.  This is not surprising since both terms refer to the study or use of genetic variation in drug responses. PGx is also often used as the more all-encompassing, or default, term when referring to the general study or use of genetic variation in drug response. ... There really isn't clear consensus (yet) on the best definitions for each term. Insight Pharma Reports, Pharmacogenomics: Delivering on the promise, 2009 

Comprises the study of variations in targets or target pathways, variation in metabolizing enzymes (pharmacogenetics) or, in the case of infectious organisms, genetic variations in the pathogen. CHI Drug Discovery Map http://www.healthtech.com/drugdiscoverymap.asp

For the purposes of this guidance, the term pharmacogenomics is defined as the use of a pharmacogenomic or pharmacogenetic test (see glossary for definitions) in conjunction with drug therapy. Pharmacogenomics does not include the use of genetic or genomic techniques for the purposes of biological product characterization or quality control (e.g. cell bank characterization, bioassays). The FDA plans to provide guidance on those uses at a future time. Pharmacogenomics also does not refer to data resulting from proteomic or metabolomic techniques.  This document is not meant to provide guidance on pharmacoproteomics or multiplexed protein analyte based technologies. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

The investigation of variations of DNA and RNA characteristics as related to drug response. ... does not include other disciplines such as proteomics and metabonomics.  E15 terminology in Pharmacogenomics, ICH, 2008 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129296.pdf  

The tools for pharmacogenomics carry the promise of achieving improved drug safety, earlier attrition rates, decreased drug development costs, a reduced drug development cycle, and resuscitation of failed drugs. Delivering on these promises will lead the way toward longer patent life and greater profits for new drugs. The challenge — and opportunity — for pharmaceutical companies is to figure out how to deploy the appropriate pharmacogenomics strategy into the drug sales model to facilitate maximum return. Can be construed as the study of the entire complement of pharmacologically relevant genes, how they manifest their variations, how these variations interact to produce phenotypes, and how these phenotypes affect drug response. A key element of pharmacogenomics is, not surprisingly, the large- scale and high throughput collection of data, including DNA sequence variations, mRNA expression analysis, enzyme kinetic assays, and cellular localization experiments. Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, c.2001http://bmir.stanford.edu/file_asset/index.php/91/BMIR-2001-0898.pdf 

Pharmacogenomics is the analysis of the effect of genomics — in particular, genetic variation (polymorphisms) — on drug response. This practice can potentially help clinicians administer more tailored treatment. The term pharmacogenetics is often used to refer specifically to tests that predict drug response; however, the terms pharmacogenetics and pharmacogenomics are often used interchangeably. 

From pharmacology + genomics.   Narrower term: pharmacogenetics Related terms:  individualized medicine, personalized medicine; Gene definitions    Proteomics  pharmacoproteomics

Pharmacogenomics ontology: http://www.obofoundry.org/cgi-bin/detail.cgi?id=pharmacogenomics Suggested ontology for Pharmacogenomics, Univ of Nancy, France 

Pharmacogenomics Research Network: A network of scientists focused on understanding how a person’s genes affect his or her response to medicines. NIH NIGMSNHLBI, NCI, NIDA, NICHDNHGRINIMH, NIAMS, ORWH http://www.nigms.nih.gov/Initiatives/PGRN/ 

Pharmacogenomics NIGMS Frequently asked questions about pharmacogenomics  http://www.nigms.nih.gov/Research/FeaturedPrograms/PGRN/Background/pgrn_faq.htm

pharmacogenomics technologies: The most critical technology is high throughput genotyping (both for large numbers of samples to be genotyped for a few variants, and a smaller number for fuller sequencing of  a large number of variants).

pharmacoglycomics: Glycosciences

pharmacokinetic- pharmacodynamic relationship:  Quantitative relationship between blood and tissue concentrations of the drug (pharmacokinetics) and the effects (pharmacodynamics) of a drug. J. Kirchheiner et. al, Pharmacogenetics- based therapeutic recommendations - ready for clinical practice? Nature Reviews Drug Discovery, 4 (8): 639- 647, August 2005

pharmacokinetics: Process of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the drugs and their metabolites in the tissues, and the elimination of the drugs and their metabolites from the body. Both the amounts and the concentrations of the drugs and their metabolism are studied. The term has essentially the same meaning as toxicokinetics but the latter term should be restricted to the study of substances other than drugs. [IUPAC Compendium]

Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance.  [MeSH, 1988]
Broader terms: DMPK, pharmacodynamics;  Narrower terms: chronopharmacokinetics, flip flop pharmacokinetics, kinetic outliers, pharmacokinetic pharmacodynamic relationship

pharmacological promiscuity:  The term 'pharmacological promiscuity' describes the activity of a single compound against multiple targets. When undesired, promiscuity is a major safety concern that needs to be detected as early as possible in the drug discovery process. The analysis of large datasets reveals that the majority of promiscuous compounds are characterized by recognizable molecular properties and structural motifs, the most important one being a basic center with a pK(a)(B)>6. These compounds interact with a small set of targets such as aminergic GPCRs; some of these targets attract surprisingly high hit rates. Can we discover pharmacological promiscuity early in the drug discovery process? Peters HU, et al Drug Discov Today. 2012 Apr;17(7-8):325-35. Epub 2012 Jan 16. http://www.ncbi.nlm.nih.gov/pubmed/22269136 

pharmacology:  The study of the origin, nature, properties, and actions of drugs and their effects on living organisms. MeSH, 1980 

Used with drugs and exogenously administered chemical substances for their effects on living tissues and organisms. It includes acceleration and inhibition of physiological and biochemical processes and other pharmacologic mechanisms of action. MeSH subheading, 1988  Narrower terms: Computational pharmacology, in silico pharmacology,

pharmacometabonomics:  Pharmaco-metabonomics is defined in the paper as 'the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures'. PHG Foundation, Pharmaco-metabonomics & personalized drug treatment, 2006  See also Metabolic engineering & profiling  metabonomics
http://www.phgfoundation.org/news/2480/    

pharmacomethylomics: Josef Straub, Pauline de Graef, Geert Trooskens, Katja Bierau, Steven de Jong, Joseph W. Bigley, Ate van der Zee, Herman Spolders and Wim MR Van Criekinge, Pharmacomethylomics: methylation profiling applied to drug resistance models, AACR Meeting Abstracts Online, 2006 http://aacrmeetingabstracts.org/cgi/content/abstract/2006/2/A95

John N. Weinstein "Pharmacogenomics: Teaching Old Drugs New Tricks" New England Journal of Medicine 343: 1408-1409, 2000  

pharmacophylogenomics:  This study applied the concept of pharmacophylogenomics, the study of genes, evolution, and drug targets, , to conduct an evolutionary survey of drug targets with respect to their subcellular localizations.  Evolutionary survey of druggable protein targets with respect to their subcellular localizations Xiaotong Wang Genome Biology and Evolution Advance Access published June 7, 2013 doi:10.1093/gbe/evt09  http://gbe.oxfordjournals.org/content/early/2013/06/07/gbe.evt092.full.pdf

David B. Searls, Pharmacophylogenomics, Genes, Evolution and Drug Targets, Nature Reviews Drug Discovery 2 ; doi:10.1038/nrd1152, 2003  

pharmacoproteomics: Once you have identified a number of proteins secreted in sera or urine, you can segregate the proteins by which are linked to early disease, the onset of metastasis, who does and does not tolerate treatment, toxic effects, and who is prone to resistance or relapse.  Fundamentally, you establish a pharmacoproteomic profile of an individual. Like pharmacogenomics, which allows researchers and clinicians to predict the response of an individual to drug treatment on the basis of his or her genetic profile, the evolving field of pharmacoproteomics allows drug developers and clinicians to further subdivide the treated population.  Randall C. Willis, ":The Matching Game" Modern Drug Discovery, 5(5): 26-35, May 2002 http://pubs.acs.org/subscribe/journals/mdd/v05/i05/html/05willis.html

Use of protein expression data to predict toxicity and understand drug mode of action.  

pharmacotyping: The individualized drug selection and dosage profiling by the health professional, based on patient's genotyping and haplotyping data for genes involved in pharmacodynamic and pharmacokinetic drug actions in the body.  Ioannis S. Vizirianakis, Challenges in Current Drug Delivery from the Potential Application of Pharmacogenomics and Personalized Medicine in Clinical Practice, Current Drug Delivery 1: 73- 80, 2004. 

phenotype standards: The characterization of phenotype is important for both the genotype- to- phenotype methods as well as the phenotype - to- genotype methods.  Phenotype is difficult to precisely define, but can be thought of as functional features of gene products, ranging in detail from molecular to the individual and population levels. Unfortunately, phenotype data is not as "digital" as sequence data, and so it is much more difficult to represent.  Nevertheless the success of pharmacogenomics depends on the establishment of standards for describing these data. Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, c.2001 http://bmir.stanford.edu/file_asset/index.php/91/BMIR-2001-0898.pdf   

phenotype-to-genotype:  Phenotype- to- genotype approaches take a different approach to pharmacogenomic discovery. Instead of identifying a family of genes in which to characterize genetic variations, investigators search for a phenotypic measure that shows significant variation.  This measure can be a clinical measure (such as the rate of clearance of a drug or the peak level of the drug for a given dose), a cellular measure (the rate of cellular uptake of a drug or the profile of gene expression) or a molecular measure (the enzymatic turnover rate of an enzyme or a substrate binding constant). Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, c.2001 http://bmir.stanford.edu/file_asset/index.php/91/BMIR-2001-0898.pdf   Compare genotype- to- phenotype

physiologically based pharmacodynamics: Physiologically based modelling of pharmacodynamics/toxicodynamics requires an a priori knowledge on the underlying mechanisms causing toxicity or causing the disease. In the context of cancer, the objective of the expert meeting was to discuss the molecular understanding of the disease, modelling approaches used so far to describe the process, preclinical models of cancer treatment and to evaluate modelling approaches developed based on improved knowledge. Modelling the genesis and treatment of cancer: the potential role of physiologically based pharmacodynamics. Steimer JL et. al Eur J Cancer. 2010 Jan;46(1):21-32. http://www.ncbi.nlm.nih.gov/pubmed/19954965

polypharmacology: "dirty drugs" "drug promiscuity" How many drug targets are there?, John P Overington, et. al, Nature Reviews Drug Discovery, 2006 http://www.nature.com/nrd/journal/v5 

predictive pharmacogenomics: Various approaches, including pharmacogenomics, that make up the emerging field of predictive medicine. These approaches allow clinicians to predict the risk of disease based on genetic testing, whether a particular therapy will be effective in a particular patient, the risk of an adverse effect, and the risk that a disease will progress in a particular manner. The technologies underlying these new approaches will change drug discovery and development, clinical trials, and diagnosis and treatment of disease. 

quantitative pharmacology: leverages model-based approaches, operates at both cultural and technical levels to integrate data and scientific disciplines so as to utilize existing knowledge while concomitantly enhancing the ability to make predictions about future experiments and results. Next-generation model-based drug discovery and development: quantitative and systems pharmacology. SR Allerheilgen, Clin Pharmacol Ther 2010 Jul ;88 (1): 135-137. Epub 2010 Jun 9. http://www.ncbi.nlm.nih.gov/pubmed/20531467 

quantitative systems pharmacology: "in the middle of October, Harvard Medical School (HMS) announced a broad initiative in systems pharmacology and NIH released a like-minded white paper, Quantitative and Systems Pharmacology in the Post-genomic Era: New Approaches to Discovering Drugs and Understanding Therapeutic Mechanisms ... what distinguishes systems pharmacology is its laser-like focus on compounds and how they perturb biological systems and pathways. How specifically do compounds—failed and successful drugs as well as others—work in the body? What are the detailed mechanisms? How are they influenced by various ‘omics? How do they vary by tissue? etc. ... The practical implications of such a compound-centric approach are exciting: new targets, new screens, new markers, new understanding of drug failure mechanisms. Indeed sophisticated drug failure analysis may be one of SP’s most promising goals and eventually most rewarding contributions."  What is (Quantitative) Systems Pharmacology? John Russell, BioIT World Jan 2012 http://www.bio-itworld.com/ issues/2012/jan/what-is- quantitative-systems- pharmacology.html

reverse pharmacology: [Masashi] Yanagisawa [Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center at Dallas] went after these receptors because they are mostly "orphan receptors"— those with no known ligand. He suspected that the ligand for many of these receptors would turn out to be a peptide hormone. The computer research yielded about 50 sequences that the group felt were likely to be G protein- coupled receptors, and then set about using those receptors as bait to capture peptide hormones, their true quarry. This strategy is known in the field as "reverse pharmacology.   "In traditional pharmacological research, the hormone is identified first," Yanagisawa said. "That hormone is then used as a tag to pull out the receptor molecule. We're doing this in reverse."  ['Hormones found that influence appetite' HHMI News Feb. 20, 1998]  http://www.hhmi.org/news/orexin.html Related terms: Pharmaceutical biology

structural pharmacogenomics: Applying structural genomics toward understanding the consequences of  single nucleotide polymorphisms (SNPs).  .

systems pharmacology: Systems Pharmacology April 29 - May 1, 2014 • Boston, MA Program | Register | 

brings a new combination of mathematical and experimental tools to bear on the discovery and analysis of therapeutic drugs.  System-level understanding of pharmacological effects will help to identify new uses for existing drugs, identify those patients most likely to benefit from mono and combination therapies, and make drug discovery and development faster, cheaper, and more predictable. Initiative in Systems pharmacology, Harvard Medical School http://isp.hms.harvard.edu/

NIGMS defines Integrative and Organ Systems Pharmacology (IOSP) as "pharmacological research using in vivo animal models or substantially intact organ systems that are able to display the integrated responses characteristic of the living organism that result from complex interactions between molecules, cells, and tissues." Such studies are important because isolated molecules and cells in vitro do not necessarily reflect the properties that they possess in vivo and cannot adequately reflect the function of intact tissues, organs, and organ systems. Speaking of Pharmacology, Integrative and Organ Systems Pharmacology: A New Initiative from the National Institute of General Medical Sciences [NIGMS], Peter C. Preusch, Molecular Interventions, 4: 72- 73, 2004 http://molinterv.aspetjournals.org/cgi/content/full/4/2/72

Bioinformatics and genomic approaches are suggesting new targets for study.  Hypotheses generated by in vitro studies or by computational biology and systems approaches to the integrative behavior of living systems need to be tested in the actual living organism.  The ability to develop genetically modified organisms has outstripped the ability to characterize the phenotypic changes in these organisms.  Interest is growing in behavioral and neurobiological phenomena that can only be studied in relatively intact systems and living organisms.  Discoveries in the areas of chemistry, genomics, and pharmacogenetics have accelerated the rate of research and have increased the demand for integrative and organ systems pharmacologists in the pharmaceutical industry.  Pharmacologists, experienced with in vivo models, form an integral part of every drug discovery and development project and are essential to assuring that only safe and efficacious lead compounds go forward to clinical trials.  New tools, such as microdialysis and imaging methods, have become available that enhance the collection efficiency and value of pharmacological data obtained in vivo.   NIGMS, SHORT COURSE: INTEGRATIVE AND ORGAN SYSTEMS PHARMACOLOGY, Apr 26, 2004, RFA-GM-05-006  http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-05-006.html 

target haplotype: Pharmacogenomics can reduce risk when used toward identifying the haplotypes of a target gene. For example. there are some beta agonists that have differential effects on haplotypes of the beta-1 receptor. In fact, some have absolutely no effect on at least one haplotype of the receptor. Uncovering such differences can reveal the degree to which a candidate compound will vary in its efficacy, and will help identify sub- populations that may benefit from the drug and others which may not benefit... In the few cases where a haplotype effect has been demonstrated, the discovery was accidental, occurring after the development of the drug. CHI Summit Pharmacogenomics report Broader term: Sequencing: haplotype

therapeutic equivalency:  The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease. MeSH, 1970

therapeutic index TI:  The ratio of the LD50 to the effective dose (ED50). How close is the dose which will kill 50% of the tested animals to the dose required for the desired effect in humans? If these two doses are very close to each other, then there is an obvious danger in using the drug with humans. [US Dept. of Justice in the matter of MDMA Scheduling, Docket No. 84- 48, 1986 www.streetdrugs.org] http://www.mninter.net/~publish/mdma.htm

translational pharmacodynamics: Guidance for the use of biomarkers in pharmaceutical development and clinical trial optimization will reduce developmental cycle time. A 'fit-for-purpose' guidance for biomarker use is considered herein when the same biomarker is applied in very different contexts in drug development and after regulatory approval. Recent approved use of renal safety biomarkers in Good Laboratory Practice studies lacks sufficient guidance for the use of these markers across the drug development pipeline. In lead optimization, renal injury biomarkers are possible anchors for promising new prodromal metabolic biomarkers, which are applied before lead candidate selection. A guidance for renal biomarker lead optimization and use in translational pharmacodynamics. Ozer JS. Drug Discov Today. 2010 Feb;15(3-4):142-7. Epub 2009 Dec 21. http://www.ncbi.nlm.nih.gov/pubmed/20026239

VGDS: Voluntary Genomic Data Submission, FDA, Draft Guidance for Industry Pharmacogenomic Data Submissions, Federal Register 68 (213): 62461- 62463, 62461-62463, Nov. 4, 2003. http://www.fda.gov/OHRMS/DOCKETS/98fr/03-27646.htm

validation - drug response phenotype: See under drug response phenotype.

Voluntary Genomic Data Submissions VGDS: The designation  for pharmacogenomic data submitted voluntarily to the FDA. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

Bibliography
American Medical Association, Pharmacogenomics 2011 http://www.ama-assn.org//ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/pharmacogenomics.page
ATSDR Glossary, Agency for Toxic Substances & Disease Registry, http://www.atsdr.cdc.gov/glossary.html 2009
EMEA, European Medicines Agency, Guidelines on Pharmacogenetics Briefing Meetings, 2008  20 plus definitions http://www.emea.europa.eu/pdfs/human/pharmacogenetics/2022704en.pdf 
Genetics Home Reference, What is Pharmacogenomics? 2013  http://ghr.nlm.nih.gov/handbook/genomicresearch/pharmacogenomics
Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.  http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 
Glossary of IRIS [Integrated Risk Information System] Terms, Environmental Protection Agency, 1999, 130+ terms http://www.epa.gov/IRIS/help_gloss.htm  
Insight Pharma Reports Pharmacogenomics: Delivering on the Promise 2009  
IUPAC, Glossary for toxicokinetics of chemicals, 365 terms. http://www.iupac.org/publications/pac/2004/pdf/7605x1033.pdf  Published Pure & Applied Chemistry 76 (5): 1033-1082, 2004
IUPAC International Union of Pure and Applied Chemistry, GLOSSARY FOR CHEMISTS OF TERMS USED IN TOXICOLOGY  2nd EDITION - IUPAC RECOMMENDATIONS 2007 Published in Pure Appl. Chem., Vol. 79, No. 7, pp. 1153-1344, 2007 http://sis.nlm.nih.gov/enviro/iupacglossary/frontmatter.html
Glossary, Toxicogenomics Research Consortium, NIEHS, US, 2003, 30 plus definitions http://www.niehs.nih.gov/dert/trc/glossary.htm  
Pelikan, Edward W.  Glossary of terms and symbols used in pharmacology, Boston University Medical School, US, 2004, about 300 definitions. http://www.bumc.bu.edu/busm-pm/inforesources/glossary/ 
Pharmacogenomics supplement, Nature Biotechnology 16, Oct. 1998  http://www.nature.com/cgi-taf/dynapage.taf?file=/nbt/journal/v16/n2s/index.html

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IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

 

 

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