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Special Issue "Personalized Medicine"

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 December 2009)

Special Issue Editors

Guest Editor
Prof. Dr. Munir Pirmohamed

NHS Chair of Pharmacogenetics, MRC Centre for Drug Safety Sciences,Department of Pharmacology, The University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK
E-Mail
Fax: +44 151 794 5540
Interests: pharmacogenomics; stratified medicines; drug safety; clinical pharmacology; alcohol dependency; alcoholic liver disease
Guest Editor
Dr. Graeme J. Sills

Division of Neurological Science, University of Liverpool, Clinical Sciences Centre for Research & Education, University Hospital Aintree, Lower Lane, Liverpool L9 7AL, UK
E-Mail
Fax: +44 151 529 5465
Interests: pharmacogenomics; metabonomics; epilepsy; antiepileptic drugs; mechanisms of action; drug metabolism; drug resistance

Special Issue Information

Dear Colleagues,

Inter-individual variation in drug response is a major hurdle to successful disease management. Some patients will respond well to the introduction of a new medication, others will achieve little or no benefit, some will get worse, many will not tolerate the new drug and an unfortunate few may experience a severe adverse reaction. This uncertainty about the outcome of treatment is a reflection of the empiricism which remains in modern medicine and which has significant social and economic consequences. The concept of personalized medicine is one in which biological information about an individual is used to optimise the diagnosis and management of their disease. It holds promise for the rational use of therapy and the avoidance of poor and potentially life-threatening outcomes. After many years of wishful predictions, we now stand on the cusp of an era of personalized medicine, with applications already emerging in several areas of clinical care and others expected to bear fruit in due course. This is in part due to the success of the Human Genome Project, an improved understanding of human biology, and the widening availability of technologies to support systems biology research. This special issue of Pharmaceuticals will highlight ongoing investigations and recent developments in the pursuit of personalized medicine in several key therapeutic arenas, with particular emphasis on genetic contributors to variation in drug responsiveness.

Graeme J. Sills, Ph. D.
Prof. Dr. Munir Pirmohamed
Guest Editors

Keywords

  • pharmacogenomics
  • pharmacogenetics
  • pharmacoproteomics
  • pharmacometabolomics
  • personalized medicine
  • combined diagnostics and therapeutics
  • systems biology
  • individualized treatment
  • therapeutics

Published Papers (5 papers)

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Research

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Open AccessArticle Implications of Inter-Individual Differences in Clopidogrel Metabolism, with Focus on Pharmacogenetics
Pharmaceuticals 2010, 3(4), 782-794; doi:10.3390/ph3040782
Received: 18 January 2010 / Revised: 9 March 2010 / Accepted: 22 March 2010 / Published: 24 March 2010
Cited by 3 | PDF Full-text (125 KB) | HTML Full-text | XML Full-text
Abstract
Increasing evidence for the role of pharmacogenetics in treatment resistance to the antiplatelet agent clopidogrel has been gained during the last years. Apart from CYP2C19 genetic polymorphisms, nongenetic factors, particularly drug-drug interactions, age and other clinical characteristics influence the interindividual variability in clopidogrel
[...] Read more.
Increasing evidence for the role of pharmacogenetics in treatment resistance to the antiplatelet agent clopidogrel has been gained during the last years. Apart from CYP2C19 genetic polymorphisms, nongenetic factors, particularly drug-drug interactions, age and other clinical characteristics influence the interindividual variability in clopidogrel response to varying degrees. The present article reviews the so far accumulated evidence on the role of pharmacogenetic traits influencing CYP-activity as determinants of the antiplatelet response to clopidogrel, and its clinical implications. The genetic variation in CYP2C19 activity seems to influence short- and long-term antithrombotic effects of clopidogrel to a substantial extent. Prediction models for clopidogrel non-responsiveness that include CYP2C19 genotyping together with relevant non-genetic risk factors are needed to be verified for their potential benefit in individualization of antithrombotic therapy. Full article
(This article belongs to the Special Issue Personalized Medicine)

Review

Jump to: Research

Open AccessReview Drug Induced Hypersensitivity and the HLA Complex
Pharmaceuticals 2011, 4(1), 69-90; doi:10.3390/ph4010069
Received: 27 October 2010 / Revised: 7 November 2010 / Accepted: 8 December 2010 / Published: 23 December 2010
Cited by 13 | PDF Full-text (152 KB) | HTML Full-text | XML Full-text
Abstract
Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated
[...] Read more.
Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity. Full article
(This article belongs to the Special Issue Personalized Medicine)
Open AccessReview The Pharmacogenomics of Anti-Hypertensive Therapy
Pharmaceuticals 2010, 3(6), 1779-1791; doi:10.3390/ph3061779
Received: 2 March 2010 / Revised: 20 May 2010 / Accepted: 26 May 2010 / Published: 1 June 2010
Cited by 3 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Hypertension is a major public health problem, but measures to reduce blood pressure and thus cardiovascular risk are complicated by the high prevalence of treatment resistance, despite the availability of multiple drugs. Drug side-effects contribute considerably to suboptimal blood pressure control. Clinicians must
[...] Read more.
Hypertension is a major public health problem, but measures to reduce blood pressure and thus cardiovascular risk are complicated by the high prevalence of treatment resistance, despite the availability of multiple drugs. Drug side-effects contribute considerably to suboptimal blood pressure control. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenomics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice. In this review we summarise the current status of hypertension pharmacogenetics from monogenic hypertension to essential hypertension and discuss the issues that need to be considered in a hypertension pharmacogenomic study. Full article
(This article belongs to the Special Issue Personalized Medicine)
Open AccessReview Beyond Genetics—Stratified and Personalised Medicines Using Multiple Parameters
Pharmaceuticals 2010, 3(5), 1637-1651; doi:10.3390/ph3051637
Received: 7 May 2010 / Accepted: 24 May 2010 / Published: 25 May 2010
Cited by 1 | PDF Full-text (127 KB) | HTML Full-text | XML Full-text
Abstract
Prescribers have been practicing stratified medicine for many years. Patient characteristics, usually non-genetic, including age, comorbidities and concomitant medications are taken into account when deciding which drug to prescribe. In addition, the majority of drugs require dose adjustments across patient subgroups, usually determined
[...] Read more.
Prescribers have been practicing stratified medicine for many years. Patient characteristics, usually non-genetic, including age, comorbidities and concomitant medications are taken into account when deciding which drug to prescribe. In addition, the majority of drugs require dose adjustments across patient subgroups, usually determined by non-genetic differences between the subgroups. Whilst pharmacogenetics hold promise for enhancing treatment stratification and even treatment individualisation, non-genetic factors will continue to be very important. Both non-genetic and genetic factors must be considered to improve understanding and quantification of the variability in treatment outcomes and to guide stratification and targeting of patient subgroups to the right drug and also to the right range of doses within that subgroup. Development of stratified medicines must consider non-genetic as well as genetic factors and, where appropriate, include stratification through optimising the dose for each patient or subgroup as well as by choosing the drug most likely to deliver efficacy to that patient or group. Full article
(This article belongs to the Special Issue Personalized Medicine)
Open AccessReview The Impact of CYP2D6 Genotyping on Tamoxifen Treatment
Pharmaceuticals 2010, 3(4), 1122-1138; doi:10.3390/ph3041122
Received: 30 December 2009 / Revised: 12 March 2010 / Accepted: 9 April 2010 / Published: 15 April 2010
Cited by 9 | PDF Full-text (241 KB) | HTML Full-text | XML Full-text
Abstract
Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly
[...] Read more.
Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly affecting the concentrations of active tamoxifen metabolites. Several studies suggest that germline genetic variants in CYP2D6 influence the clinical outcomes of patients treated with adjuvant tamoxifen. Here, we review the existing data relating CYP2D6 genotypes to tamoxifen efficacy. Full article
(This article belongs to the Special Issue Personalized Medicine)

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