Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

Gardiner, Sharon J.; Begg, Evan J.

doi:10.1124/pr.58.3.6

Cited by 358 publications

(287 citation statements)

References 867 publications

(983 reference statements)

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“…Similarly, the AUC following the administration of equal doses of pantoprazole in PM was sixfold higher than NM and IM [43,44]. Although reports have documented the impact of CYP2C19 genotype on PK for both rabeprazole [40,45–49] and esomeprazole [50,51], these associations with PK parameters such as AUC were of smaller magnitude than the effects reported for other PPIs, suggesting less influence of CYP2C19 genotype on these newer generations PPIs.…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

181

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

181

172

View full text Add to dashboard Cite

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“…The most studied gene family so far is the cytochrome P450 enzyme [5][6][7] (for more details see Table 2). The genetic variability observed in this gene family has been associated with differences in drug metabolism in several pathologies, such as cancer, cardiovascular diseases and rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

“…The genetic variability observed in this gene family has been associated with differences in drug metabolism in several pathologies, such as cancer, cardiovascular diseases and rheumatoid arthritis. [5][6][7][8] There is one SNP in CYP2C9 that causes an amino acid change that modify the ability of the enzyme to metabolize the anticoagulant warfarin. 9 This genetic variation has important implications in the dose a patient will receive of warfarin depending on the genetic background of the individual.…”

Section: Introductionmentioning

confidence: 99%

The impact of microRNAs and alternative splicing in pharmacogenomics

2009

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“…This variation can result from genetic, environmental, physiological, and pathophysiological factors such as age, gender, circadian rhythm, diet, and concomitantly administered drugs and health foods. [1,2] Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes are known to be associated with these individual differences. [1] SNPs are unique genetic markers between individuals that contribute in significant ways to the determination of human variation such as personality, behavior and disease susceptibility.…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes are known to be associated with these individual differences. [1] SNPs are unique genetic markers between individuals that contribute in significant ways to the determination of human variation such as personality, behavior and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and the production of any adverse drug reactions.…”

Section: Introductionmentioning

confidence: 99%

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Kim

Lee

et al. 2016

Transl Clin Pharmacol

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Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 significant SNPs (P < 0.01) in C max , 135 significant SNPs (P < 0.01) in T max and 85 significant SNPs (P < 0.01) in AUC inf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on C max and AUC inf . These results could provide information of possible candidate genes for personalized simvastatin therapy.

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Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

Cited by 358 publications

References 867 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

The impact of microRNAs and alternative splicing in pharmacogenomics

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

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