Association of CYP2C19 Polymorphisms and Lansoprazole-Associated Respiratory Adverse Effects in Children

Lima, John J.; Lang, Jason E.; Mougey, Edward B.; Blake, Kathryn; Gong, Yan; Holbrook, Janet T.; Wise, Robert A.; Teague, W. Gerald

doi:10.1016/j.jpeds.2013.03.017

Cited by 47 publications

(60 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, two small studies point to the possibility of such a link. Lima et al evaluated the association between CYP2C19 genotype and respiratory adverse events including upper respiratory tract infections and sore throats, using data from a clinical trial of pediatric patients who were treated with lansoprazole [97]. Results of this study showed that the average plasma concentrations in IM/PM (defined as having ≥ one * 2, *3, *8 , or * 9 alleles; N = 45) were higher than NM (without no function alleles, N = 91) (207 ± 179 ng/mL vs 132 ± 141 ng/mL ( p = 0.04)).…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…At 6 months, IM/PM phenotype was associated with worsened asthma as compared to NM phenotype (+0.16 vs. −0.13; p = 0.02) and placebo (+0.16 vs. −0.23; p < 0.01) at 6 months. The authors proposed that the worsening asthma control in IM/PM at 6 months may be due to upper respiratory tract infections, which was previously documented to be higher [97] within the same cohort with IM/PM phenotype .…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

See 1 more Smart Citation

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

Self Cite

181

172

View full text Add to dashboard Cite

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.

show abstract

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

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

Self Cite

181

172

View full text Add to dashboard Cite

show abstract

“…Mean plasma concentrations were significantly higher in poor versus (n=23, 207±179 ng/mL) extensive (n=33, 132±141 ng/mL) metabolizers (P=0.04). If these findings are replicated in an independent sample, the results may be clinically meaningful as a dosage adjustment may be performed to mitigate the occurrence of these side effects in patients classified as poor metabolizers [75].…”

Section: Pulmonary and Allergy Asthmamentioning

confidence: 87%

“…In a genetic substudy, 279 of the 306 aforementioned participants provided DNA for analysis [75]. The frequency of adverse events with lansoprazole was evaluated in children with single-nucleotide polymorphisms (SNPs) in CYP2C19 as this gene may affect lansoprazole clearance and exposure.…”

Section: Pulmonary and Allergy Asthmamentioning

confidence: 99%

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology

Paul¹

2012

Advances in Pediatrics

View full text Add to dashboard Cite

Significant advancements have been made in pediatric therapeutics and pharmacology over the last two years. In the United States, passage of the Food and Drug Administration Safety and Innovation Act has made the Best Pharmaceuticals for Children Act and Pediatric Research Equity Act permanent, and ensured that studies will be conducted in neonates. In Europe, the Pediatric Regulation, which went into effect in early 2007, has also provided a framework encouraging an expansion of pediatric research. Because of such regulatory involvement, a greater number of studies are being performed, and more pediatric dosing, efficacy, and safety information is being incorporated into product labels. The goal of this publication is to highlight important advancements made in the field of pediatric pharmacology, toxicology, and therapeutics from

show abstract

“…The study was designed so that participants had at least 2 weeks between the test protocols to allow for complete recovery, but not more than a month, to reduce chances of participants showing a change in respiratory tests' outcomes unrelated to the experimental design, and in accordance with the American Thoracic Society guidelines (2).…”

Section: Fev 1 Can Be Associated With Reduced Values After Vigorous Ementioning

confidence: 99%