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Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.

Publication ,  Journal Article
Lima, JJ; Lang, JE; Mougey, EB; Blake, KB; Gong, Y; Holbrook, JT; Wise, RA; Teague, WG
Published in: J Pediatr
September 2013

OBJECTIVE: To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. STUDY DESIGN: Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. RESULTS: The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). CONCLUSIONS: Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.

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Published In

J Pediatr

DOI

EISSN

1097-6833

Publication Date

September 2013

Volume

163

Issue

3

Start / End Page

686 / 691

Location

United States

Related Subject Headings

  • Respiratory Tract Infections
  • Proton Pump Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharyngitis
  • Pediatrics
  • Odds Ratio
  • Male
  • Logistic Models
  • Lansoprazole
  • Humans
 

Citation

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Lima, J. J., Lang, J. E., Mougey, E. B., Blake, K. B., Gong, Y., Holbrook, J. T., … Teague, W. G. (2013). Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr, 163(3), 686–691. https://doi.org/10.1016/j.jpeds.2013.03.017
Lima, John J., Jason E. Lang, Edward B. Mougey, Kathryn B. Blake, Yan Gong, Janet T. Holbrook, Robert A. Wise, and W. G. Teague. “Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.J Pediatr 163, no. 3 (September 2013): 686–91. https://doi.org/10.1016/j.jpeds.2013.03.017.
Lima JJ, Lang JE, Mougey EB, Blake KB, Gong Y, Holbrook JT, et al. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr. 2013 Sep;163(3):686–91.
Lima, John J., et al. “Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.J Pediatr, vol. 163, no. 3, Sept. 2013, pp. 686–91. Pubmed, doi:10.1016/j.jpeds.2013.03.017.
Lima JJ, Lang JE, Mougey EB, Blake KB, Gong Y, Holbrook JT, Wise RA, Teague WG. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr. 2013 Sep;163(3):686–691.
Journal cover image

Published In

J Pediatr

DOI

EISSN

1097-6833

Publication Date

September 2013

Volume

163

Issue

3

Start / End Page

686 / 691

Location

United States

Related Subject Headings

  • Respiratory Tract Infections
  • Proton Pump Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharyngitis
  • Pediatrics
  • Odds Ratio
  • Male
  • Logistic Models
  • Lansoprazole
  • Humans