Longitudinal pharmacometabonomics for predicting patient responses to therapy: drug metabolism, toxicity and efficacy

Nicholson, Jeremy K.; Everett, Jeremy R.; Lindon, John C.

doi:10.1517/17425255.2012.646987

Cited by 61 publications

(53 citation statements)

References 15 publications

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“…A further evolving concept is that of longitudinal pharmacometabonomics, where metabolic profiling is undertaken throughout a 'patient journey', in order to be better able to predict patient outcomes. [57] Finally, a host of exciting, recent studies have used genome--wide association studies (GWAS) to relate genetic variation with human blood, serum and urine metabolite profiles on a large scale. [58--61] The linkage of variation of metabolite profiles with genetic as opposed to environmental variation provides new opportunities to link metabolic profiles to disease onset and treatment and the prediction of drug effects, via previous GWAS associations with these factors.…”

Section: Future Perspectivesmentioning

confidence: 99%

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Everett¹

2015

Pharmacogenomics

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/ SummaryPharmacogenomics is now over 50 years old and has had some impact in clinical practice, through its use to select patient subgroups who will enjoy efficacy without side effects when treated with certain drugs. However, pharmacogenomics, has had less impact than initially predicted. One reason for this is that many diseases, and the way in which the patients respond to drug treatments, have both genetic and environmental elements. Pure genomics is almost blind to the environmental elements. A new methodology has emerged, termed pharmacometabonomics that is concerned with the prediction of drug effects through the analysis of predose, biofluid metabolite profiles, which reflect both genetic and environmental influences on human physiology. In this review we will cover what pharmacometabonomics is, how it works, what applications exist and what the future might hold in this exciting new area

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Section: Future Perspectivesmentioning

confidence: 99%

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Everett¹

2015

Pharmacogenomics

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“…29 It is also clear that there is a complex and close interaction between the operation of the human genome and our microbiome and there is an explosion of interest in this area recently. 58,74,83,84,[90][91][92][93][94][95][96][97][98][99][100][101]102 Metabonomics is exceptional in its ability to simultaneously sample information on the metabolic products of the human genome as well as our microbiome. We therefore expect that improved personalized medicine can be achieved with the help of information from metabonomics, which is distinguished from human genomics by two critical points: (i) it samples both genetic and environmental information and (ii) it reports on the actual physiological state of a person as opposed to a state that might exist in the future.…”

Section: Future Prospects For Pharmacometabonomicsmentioning

confidence: 99%

“…107,108 This has led to the emergence of the concept of longitudinal pharmacometabonomics to assist with the prediction of patients' responses over time as they progress through a treatment regime. 97 …”

Section: Future Prospects For Pharmacometabonomicsmentioning

confidence: 99%

Pharmacometabonomics and personalized medicine

2013

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Background: Pharmacometabonomics is a new branch of science, first described in 2006 and defined as 'the prediction of the effects of a drug on the basis of a mathematical model of pre-dose metabolite profiles'. Pharmacometabonomics has been used to predict drug metabolism, pharmacokinetics (PK), drug safety and drug efficacy in both animals and humans and is complementary to both pharmacogenomics (PGx) and pharmacoproteomics. Methods: A literature review using the search terms pharmacometabonomics, pharmacometabolomics, pharmacometabonomics, pharmaco-metabolomics and the singular form of all those terms was conducted in October 2012 using PubMed and Web of Science. The review was updated until mid April 2013. Results: Since the original description of pharmacometabonomics in 2006, 21 original publications and eight reviews have emerged, covering a broad range of applications from the prediction of PK to the prediction of drug metabolism, efficacy and safety in humans and animals. Conclusions: Pharmacometabonomics promises to be an important new approach to the delivery of personalized medicine to improve both drug efficacy and safety for patients in the future. Pharmacometabonomics is particularly powerful as it is sensitive to both genetic and environmental factors such as diet, drug intake and most importantly, a person's microbiome. PGx is now over 50 years old and although it has not achieved as much as some hoped, it is starting to have important applications in personalized medicine. We predict that pharmacometabonomics will be equally important in the next few decades and will be both valuable in its own right and complementary to pharmacoproteomics and PGx.

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“…Further investigations will be required to demonstrate the broader utility of this approach for the general patient population and also to follow and predict optimal long term treatment. [18] It is clear that pharmacometabonomics is complementary to pharmacogenomics and therefore the integration of the two technologies will be both powerful [19] and could provide more insight into mechanisms underlying individual variation in drug response.…”

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The Role of Pharmacometabonomics in Predicting Drug Pharmacokinetics

Varshavi

Everett

2016

Int. J. Pharmacokinet.

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Individual variability in drug response is a key challenge in current clinical practice and in drug discovery and development. Pharmacological response is closely associated with drug concentration at the site of action and therefore knowledge of drug pharmacokinetics is vital to delivering effective therapy. In addition to genetic polymorphisms, environmental factors also play an important role in determining drug efficacy, safety, metabolism and pharmacokinetics. The newly emerging field of pharmacometabonomics uses information from pre-dose metabolite profiles to predict individual drug responses, can be sensitive to both genetic and environmental factors and thus has great promise to help the future delivery of personalized medicine. This article introduces pharmacometabonomics and covers its application to the prediction of pharmacokinetics. EditorialPersonalised or stratified therapy is a key goal for 21 st century medicine in order to maximize therapeutic efficacy and minimize the likelihood of adverse drug reactions for groups of patients. In addition, personalised medicine has the potential to substantially enhance the process of drug discovery and development.[1] Thus far, personalized medicine has been mainly based on pharmacogenomics (PG), where an individual's genetic profile is used to

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Longitudinal pharmacometabonomics for predicting patient responses to therapy: drug metabolism, toxicity and efficacy

Cited by 61 publications

References 15 publications

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Pharmacometabonomics and personalized medicine

The Role of Pharmacometabonomics in Predicting Drug Pharmacokinetics

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