Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions

Phillips, Kathryn A.; Veenstra, David L.; Oren, Eyal; Lee, Jane K.; Sadée, Wolfgang

doi:10.1001/jama.286.18.2270

Cited by 637 publications

(313 citation statements)

References 64 publications

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“…Unfortunately, up to now, many liability genes explain less than 10% of the total variance, in the case of mood disorders as in many other fields of medicine, both for efficacy 2,51-55 and for side effect prediction. 56 Should we stop all our pharmacogenetic research then? Of course not, but knowledge is not a dichotomous issue, and partial information could be available at the beginning of the trial.…”

Section: Ethics Of Pharmacogenetics Beneficencementioning

confidence: 99%

Ethical problems in pharmacogenetic studies of psychiatric disorders

Serretti

Artioli

2006

Pharmacogenomics J

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Section: Ethics Of Pharmacogenetics Beneficencementioning

confidence: 99%

Ethical problems in pharmacogenetic studies of psychiatric disorders

Serretti

Artioli

2006

Pharmacogenomics J

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“…Ferner spielen das Ausmaß der Affinität und eine eventuelle Inhibition eine Rolle (13). Vor allem für die polymorph exprimierten Enzyme CYP 2C9, CYP 2C19 und CYP 2D6 liegen Untersuchungen zur klinischen Relevanz vor (3,15,20) Ex-vivo lässt sich beispielsweise die Aktivität der ThiopurinMethyltransferase, bei der eine Defizienz in der heterozygoten Form bei etwa 10% der Bevölkerung vorliegt, im Plasma oder die der Alkohol-Dehydrogenase bestimmen (10). Dieses Verfahren wird allerdings nur in wenigen Zentren in Deutschland durchgeführt.…”

Section: Das Cytochrom-p450-system Und Seine Bedeutung Bei Arzneimittunclassified

Adverse drug reactions

Collette

2002

Dtsch med Wochenschr

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“…When the parent drug is pharmacologically active, impaired enzyme function may increase the risk of developing adverse drug reactions (ADRs). For example, Phillips et al found that 59 % of drugs cited in ADR studies are, at least partially, metabolized by enzymes with reduced function [5]. Likewise, when metabolization results in inactivation of a parent drug, higher than normal enzyme activity may cause standard drug therapy to fail.…”

Section: Introductionmentioning

confidence: 99%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes, as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques.In this review, we provide a comprehensive overview of available methods using dried blood spots, hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or dried blood spots, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non-or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice. 4 Key Points Phenotyping by administration of a selective probe drug, followed by determination of a specific phenotyping metric, allows to assess the in vivo enzyme activity of CYP450 enzymes, taking into account genetic, non-genetic and environmental influencing factors. In addition to classical sampling techniques, such as blood or urine collection, reliable phenotyping procedures for several clinically relevant CYP450 enzymes are currently available for oral fluid, breath and dried blood spots.

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Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions

Cited by 637 publications

References 64 publications

Ethical problems in pharmacogenetic studies of psychiatric disorders

Ethical problems in pharmacogenetic studies of psychiatric disorders

Adverse drug reactions

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

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