Lansoprazole Is Associated with Worsening Asthma Control in Children with the <i>CYP2C19</i> Poor Metabolizer Phenotype

Lang, Jason E.; Holbrook, Janet T.; Mougey, Edward B.; Wei, Christine; Wise, Robert A.; Teague, W. Gerald; Lima, John J.

doi:10.1513/annalsats.201408-391oc

Cited by 25 publications

(23 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study by Lang et al [98] investigated the association between CYP2C19 genotype and asthma control (assessed by Asthma Control Questionnaire (ACQ)) in pediatric patients who were classified as IM/PM or NM and were treated with lansoprazole. 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.…”

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

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%

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

“…In a subsequent genetic sub-study, we showed that participants with IM or PM had significantly higher lansoprazole levels compared to NM and were significantly more likely to suffer respiratory adverse events related to URI and strep/sore throat [64]. These same PM participants developed worse asthma controlled (triggered by URI) compared to NM after 4 months on conventional PPI dosing [71]. Conventional dosing of PPI in these IM and PM patients is likely to improve GERD symptoms at the cost of greater risk of URIs.…”

Section: Discussionmentioning

confidence: 84%

Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods

Tang

Blake

Lima

et al. 2019

Contemporary Clinical Trials

Self Cite

View full text Add to dashboard Cite

Asthma causes enormous suffering and cost for children in the US and around the world [1-3]. Comorbid gastroesophageal reflux disease (GERD) makes asthma management more difficult due to increased symptoms. Proton pump inhibitor (PPI) drugs are effective at improving to GERD symptoms, however they have demonstrated only modest and variable effects on asthma control in the setting of co-morbid GERD. Importantly, PPI metabolism and efficacy depend on CYP2C19 genotype. The Genotype Tailored Treatment of Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA) study is a randomized, double-blind, placebo-controlled trial to determine if genotype-tailored PPI dosing improves asthma symptoms among children with inadequately controlled asthma and GERD symptoms. This study has an innovative design to both assess the efficacy of genotype-tailored PPI dosing and perform pharmacokinetic modeling of the oral PPI Lansoprazole. Children ages 6-17 years old with clinician-diagnosed asthma and mild GERD symptoms will submit a saliva sample for CYP2C19 genotyping. Participants will undergo a two-step randomization to: (1) genotype-tailored versus conventional dosing of open-label oral lansoprazole for pharmacokinetic modeling, and (2) genotype-tailored lansoprazole daily versus placebo for 24 weeks to determine the effect of genotype-tailored PPI dosing on asthma control. Measures of asthma control, spirometry, and nasal washes during acute illnesses will be collected at 8-week intervals throughout the study. GenARA will better define the effects of CYP2C19 genotype on the dose response of lansoprazole in children and adolescents and assess if a novel dosing regimen improves GERD and asthma control. Tang et al.

show abstract

“…We appreciate the interest of Dr. Sukhovershin, Dr. Ghebremariam, and Dr. Cooke in our recent report about worsening asthma control among children taking lansoprazole who have the CYP2C19 poor metabolizer phenotype (1). The authors correctly point out that we found that these children developed worse asthma symptoms after 5 months of lansoprazole therapy.…”

Section: From the Authorsmentioning

confidence: 75%

“…I read with great interest the study "Vigorous exercise can cause abnormal pulmonary function in healthy adolescents," recently published by Abosaida and colleagues (1).…”

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

confidence: 99%

Reply: Worsening Asthma Control in Children Taking Lansoprazole: Possible Mechanisms

Lang

Holbrook

Lima³

2015

Annals ATS

Self Cite

View full text Add to dashboard Cite

Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype

Cited by 25 publications

References 41 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods

Reply: Worsening Asthma Control in Children Taking Lansoprazole: Possible Mechanisms

Contact Info

Product

Resources

About