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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
ADAPT
September 19-21, 2012 • Washington, DC Program | Register | Download
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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 Google
= about 163 May 8, 2003; about 315 June 10, 2004, about 668 Aug. 17, 2005; about
942 Nov 10, 2006 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 Google
= about 5,670 Aug. 17, 2005; about 30,800 Nov 10, 2006 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.
Google = about 24 Sept. 4, 2003; about 22 June 7, 2004; about 76 Nov 10, 2006
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. Google
= about 1, 090 May 7, 2003; about 2,730 June 7, 2004; about 42,600 Nov 10, 2006
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 Google - about 7 July 17, 2002;
about 29 June 7, 2004; about 47 Nov 10, 2006, about 128 May 13, 2009 Related
terms: Biomarkers; Cancer
genomics
organ systems
pharmacology: See integrative and organ systems pharmacology
Personalized
Medicine Executive Summit: Implementing
Personalized Medicine September 19-21, 2012 •
Washington, DC Program | Register | Download
Brochure
personalized
medicine:
Personalized health care is envisioned as a system in which doctors,
pharmacists, and other health care providers customize treatment and management
plans for individuals. It will be founded upon vast amounts of information that
will be readily accessible at clinics and hospital bedsides. The driver is the
many applications of information technology that have blossomed during the
biomedical revolution. For example, tools like electronic capture will allow
easy dissemination and flow of data about medical history, genetic variability,
and even patient preferences. ... This is already happening. Personalized
Healthcare, Pathways, Opportunities, Resources, HHS 2007 http://www.hhs.gov/myhealthcare/news/presonalized-healthcare-9-2007.html
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
Google
= about 6,410 May 7, 2003; about 18,300 June 7, 2004, about 453,000 April 24,
2006; about 468,000 Nov 10, 2006; about 553,000 Sept 29, 2008. 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
Google May 21,
2004 pgx and pharmacogenomics = about 326 pgx and pharmacogenetics
about 329
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
Google = about 19 Nov
5, 2005, about 38 Oct. 25, 2006, about 471 May 13, 2009
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. Google = about
24,700 May 7, 2003; about 112,000 June 7, 2004; 1,500,000 Nov 10, 2006, about
1,180,000 Dec 12, 2008 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
The study of how an individual's genetic inheritance affects the body's response to
drugs and holds the promise that drugs might one day be tailor- made for individuals and adapted to each person's own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.
Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of
genes, proteins, and single nucleotide polymorphisms.
[Human Genome Project Information, Pharmacogenomics, Oak Ride National Lab,
2001] http://www.ornl.gov/hgmis/medicine/pharma.html
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. Google = about
29,200 May 7, 2003; about 117,000 June 7, 2004; about 387,000 Apr. 25, 2005,
about 1,670,000 Oct. 25, 2006, about 816,000 Dec 12, 2008 Narrower term:
pharmacogenetics
Related terms: individualized medicine, personalized medicine; Gene definitions
Proteomics pharmacoproteomics
Promise of pharmacogenomics,
National Center for Biotechnology
Information, US, 2001 http://www.ncbi.nlm.nih.gov/About/primer/pharm.html
Part of NCBI's Science Primer
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 NIGMS, NHLBI,
NCI, NIDA,
NICHD, NHGRI, NIMH,
NIAMS, ORWH
http://www.nigms.nih.gov/Initiatives/PGRN/
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/
http://www.nature.com/nm/journal/v12/n5/full/nm0506-510.html
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 Google = about 13 July 11, 2002;
about 91 July 14, 2003; about 131 June 7, 2004, about 106 Aug. 15, 2005, about
125 Oct. 25, 2006, about 174 Dec 12, 2008
pharmacophylogenomics:
David B. Searls, Pharmacophylogenomics,
Genes, Evolution and Drug Targets, Nature
Reviews Drug Discovery 2 ; doi:10.1038/nrd1152, 2003 Google = about
21 Mar. 3, 2004, about 70 Aug.
15, 2005 ,about 181 Oct. 25, 2006, about 174 Dec 12, 2008
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. Google
= about 402 Sept. 5, 2003; about 469 June 7, 2004; about 21,500 Nov. 5,
2005; about 15,600 Nov 10, 2006
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
ADME: Drug safety & pharmacovigilance
predictive biomedicine:
Molecular medicine
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.
predictive proteomics: Proteomics
categories
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:
[Molecular Pharmacology} is combined
with information about how effects of drugs on different organs and tissues are
integrated to produce a therapeutic or toxic effect. Molecular and Systems
Pharmacology, Emory University, 2006 http://biomed.emory.edu/programs/program_msp.cfm
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
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
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
Insight pharma Reports Advances
in Lead Optimization Accelerating Drug Discovery and Development
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IUPAC, Glossary for toxicokinetics of
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IUPAC International
Union of Pure and Applied Chemistry, GLOSSARY FOR CHEMISTS OF TERMS USED
IN TOXICOLOGY Clinical Chemistry Division, Commission on Toxicology, Recommendations. Pure and Appl. Chem., 65 (9):
2003- 2122, 1993. 1200+ definitions. http://www.iupac.org/reports/1993/6509duffus/index.html30
plus definitions
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
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Pharmacogenomics supplement, Nature Biotechnology 16, Oct. 1998 http://www.nature.com/cgi-taf/dynapage.taf?file=/nbt/journal/v16/n2s/index.html
Alpha
glossary index
How
to look for other unfamiliar terms
IUPAC definitions are reprinted with the
permission of the International Union of Pure and Applied Chemistry.
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