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Safety and Pharmacodynamics of Lansoprazole in Patients with Gastroesophageal Reflux Disease Aged <1 Year

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Abstract

Background: The use of proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in pediatric patients <1 year of age is increasing. However, few studies with PPIs have been reported in such patients.

Objectives: To assess the effect of once-daily lansoprazole on safety and to characterize the pharmacodynamic profile of lansoprazole in a subset of subjects <1 year of age. The effect of lansoprazole on predefined GERD-associated symptoms was also assessed.

Methods: Two phase I, single- and repeated-dose, randomized, parallel-group, open-label, multicenter studies were performed. Both studies involved either a 7- or 14-day pre-treatment period, with a dose administration period of 5 days, and a follow-up period of 30 days for adverse events collection. A total of six investigative sites were involved: four university hospital/medical centers (three in Poland, one in the US), one large regional medical center (Poland), and one private practice (US). The studies involved 24 neonates (≤28 days of age) and 24 infants (>28 days but <1 year of age) with GERD-associated symptoms diagnosed by medical history and the clinical judgment of the treating physician. Eligible subjects were randomized to receive either lansoprazole 0.5 or 1.0 mg/kg/day (neonates), or 1.0 or 2.0 mg/kg/day (infants), for 5 days.

Safety and pharmacodynamic parameters were the primary outcome measures. Safety and GERD symptoms were assessed in all participants. Intragastric/intraesophageal pH monitoring was performed in a subset of six neonates and six infants at baseline and on dose administration days 1 and 5.

Results: Over 5 days of daily dose administration, lansoprazole was well tolerated in neonates and infants. Four neonates and one infant experienced mild to moderate treatment-related adverse events during the dose administration period. One neonate experienced a serious adverse event that was unrelated to treatment. Lansoprazole increased the percentage of time that intragastric pH was above 3, 4, 5, and 6 over the 24-hour post-dose period on days 1 and 5 when compared with baseline. Mean 24-hour integrated gastric acidity decreased from baseline to day 5 in both populations. The daily number of episodes of regurgitation/vomiting was lower than at baseline among neonates after 5 days of lansoprazole treatment; among infants, both the prevalence and the average daily number of episodes of several individual GERD-associated symptoms were lower than at baseline.

Conclusions: After 5 days of open-label administration, lansoprazole was well tolerated and increased intragastric pH in pediatric subjects <1 year of age. A decrease in the frequency of GERD symptoms was also observed.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 2001; 32Suppl. 2: 1–31S

    Article  Google Scholar 

  2. Vandenplas Y, Salvatore S, Hauser B. The diagnosis and management of gastro-oesophageal reflux in infants. Early Hum Dev 2005 Dec; 81: 1011–24

    Article  PubMed  Google Scholar 

  3. Cezard JP. Managing gastro-oesophageal reflux disease in children. Digestion 2004; 69Suppl. 1: 3–8

    Article  PubMed  CAS  Google Scholar 

  4. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux during infancy: a pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997 Jun; 151(6): 569–72

    Article  PubMed  CAS  Google Scholar 

  5. Nelson SP, Chen EH, Syniar GM, et al. One-year follow-up of symptoms of gastroesophageal reflux during infancy. Pediatric Practice Research Group. Pediatrics 1998 Dec; 106(6): E67

    Article  Google Scholar 

  6. Martin AJ, Pratt N, Kennedy JD, et al. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics 2002 Jun; 109(6): 1061–7

    Article  PubMed  Google Scholar 

  7. Gremse DA. GERD in the pediatric patient: management considerations. MedGenMed 2004 May; 6(2): 13

    PubMed  Google Scholar 

  8. Chiba N, De Gara CJ, Wilkinson JM, et al. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997 Jun; 112: 1798–810

    Article  PubMed  CAS  Google Scholar 

  9. Cucchiara S, Minella R, Iervolino C, et al. Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis. Arch Dis Child 1993; 69: 655–9

    Article  PubMed  CAS  Google Scholar 

  10. Reilly JP. Safety profile of proton pump inhibitors. Am J Health Syst Pharm 1999 Dec; 56Suppl. 4: 11S–7S

    Google Scholar 

  11. Barron JJ, Hiangkiat T, Spalding J, et al. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr 2007 Oct; 45(4): 421–7

    Article  PubMed  CAS  Google Scholar 

  12. Jadcherla SR. Gastroesophageal reflux in the neonate. Clin Perinatol 2002 Mar; 29(1): 135–58

    Article  PubMed  Google Scholar 

  13. Zhang W, Kukulka M, Witt G, et al. Age-dependent pharmacokinetics of lansoprazole in neonates and infants. Pediatr Drugs 2008; 10(4): 265–74

    Article  CAS  Google Scholar 

  14. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Adopted by the 18th World Medical Assembly, Helsinki, 1964 and amended by the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 [online]. Available from URL: http://www.wma.net/e/policy/b3.htm [Accessed 2008 Jun 3]

  15. Strobel CT, Byrne WJ, Ament ME, et al. Correlation of esophageal lengths in children with height: application to the Tuttle test without prior esophageal manometry. J Pediatr 1979 Jan; 94(1): 81–4

    Article  PubMed  CAS  Google Scholar 

  16. Fiedorek S, Tolia V, Gold BD, et al. Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and non-erosive gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2005 Mar; 40(3): 319–27

    Article  PubMed  CAS  Google Scholar 

  17. Croom KF, Scott LJ. Lansoprazole: in the treatment of gastro-oesophageal reflux disease in children and adolescents. Drugs 2005; 65(15): 2129–35

    Article  PubMed  CAS  Google Scholar 

  18. Gunasekaran T, Gupta S, Gremse D, et al. Lansoprazole in adolescents with gastroesophageal reflux disease: pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability. J Pediatr Gastroenterol Nutr 2002; 35Suppl. 4: S327–35

    Article  PubMed  CAS  Google Scholar 

  19. Gremse D, Winter H, Tolia V, et al. Pharmacokinetics and pharmacodynamics of lansoprazole in children with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2002; 35Suppl. 4: S319–26

    Article  PubMed  CAS  Google Scholar 

  20. Faure C, Michaud L, Shaghaghi EK, et al. Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis. Aliment Pharmacol Ther 2001 Sep; 15(9): 1397–402

    Article  PubMed  CAS  Google Scholar 

  21. Tran A, Rey E, Pons G, et al. Pharmacokinetic-pharmacodynamic study of oral lansoprazole in children. Clin Pharmacol Ther 2002 May; 71(5): 359–67

    Article  PubMed  CAS  Google Scholar 

  22. Franco MT, Salvia G, Terrin G, et al. Lansoprazole in the treatment of gastro-oesophageal reflux disease in childhood. Dig Liver Dis 2000 Nov; 32(8): 660–6

    Article  PubMed  CAS  Google Scholar 

  23. Cucchiara S, Borreli O, Gaudiello G, et al. Lansoprazole in children with severe gastroesophageal reflux disease: effect on gastric acidity, esophagitis and clinic outcome [abstract]. Gastroenterology 1999; 116(4): A142

    Google Scholar 

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Acknowledgments

These studies were sponsored by TAP Pharmaceutical Products Inc., Lake Forest, IL, USA (ClinicalTrials.gov identifiers: NCT00174928 and NCT00220818). Writing support was provided by Rx Communications (UK) and funded by TAP Pharmaceutical Products Inc.

Dr Springer is a consultant to TAP Pharmaceutical Products Inc. All other authors of this paper are employees of TAP Pharmaceutical Products Inc.

The authors would like to thank all investigators who participated in these studies. We also wish to thank the Clinical Research Organization (Kendle International Inc.) for coordinating this study, Kathleen Ruesch for her assistance in managing the study, as well as Rx Communications (UK) for its assistance in the preparation of this article. Weijiang Zhang, TAP Pharmaceutical Products Inc., and Professor Wanda Furmaga-Jablonska, University Children’s Hospital, Lublin, Poland, were also contributors to this article.

The authors would like to thank the six investigators for enrolling and caring for their patients. Special thanks to Professor W. Furgmaga-Jablonska (University Children’s Hospital, Lublin, Poland); Dr M. Springer (Louisiana State University Health Sciences, Shreveport, LA, USA); Professor M. Kaczmarski (Medical University of Bialystok, Bialystok, Poland); Professor K. Fyderek (Polish American Institute of Pediatrics, Krakow, Poland); and Dr I. Haddad (Private Practice, Youngstown, OH, USA).

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Authors and Affiliations

  1. Children’s Clinical Research Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA

    Margaret Springer

  2. TAP Pharmaceutical Products Inc., 675 North Field Drive, Lake Forest, Illinois, 60045, USA

    Stuart Atkinson, Janine North & Marsha Raanan

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  1. Margaret Springer
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  2. Stuart Atkinson
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Correspondence to Stuart Atkinson.

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Springer, M., Atkinson, S., North, J. et al. Safety and Pharmacodynamics of Lansoprazole in Patients with Gastroesophageal Reflux Disease Aged <1 Year. Pediatr-Drugs 10, 255–263 (2008). https://doi.org/10.2165/00148581-200810040-00004

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