Digestive Diseases and Sciences

, Volume 56, Issue 2, pp 425–434 | Cite as

Pharmacodynamics and Safety of Pantoprazole in Neonates, Preterm Infants, and Infants Aged 1 Through 11 Months with a Clinical Diagnosis of Gastroesophageal Reflux Disease

  • Jaroslaw Kierkus
  • Wanda Furmaga-Jablonska
  • Janice E. Sullivan
  • Elmer S. David
  • Dan L. Stewart
  • Natalie Rath
  • Caifeng Fu
  • Wenjin Wang
  • Mary K. Maguire
  • Gail M. Comer
Original Article

Abstract

Background

Limited data on proton pump inhibitors in infants led regulatory agencies to request sponsors to conduct pediatric studies.

Aim

To determine the pharmacodynamic response to pantoprazole in infants with GERD to aid the dose selection for an efficacy study.

Methods

In two open-label studies, neonates and preterm infants (study 1, ~1.2 mg/kg [high dose]) and infants 1 through 11 months (study 2, ~0.6 [low dose] or ~1.2 mg/kg [high dose]) received once-daily pantoprazole. Twenty-four-hour dual-electrode pH-metry parameters were compared between predose and steady state (≥5 days) (two-sided paired t test). Treatment was administered for ≤6 weeks.

Results

In studies 1 and 2, 21 and 24 patients, respectively, were enrolled for pharmacodynamic evaluation. The high dose provided similar responses in the two studies and improved these parameters significantly: mean gastric pH and percent time gastric pH > 4 increased (p < 0.05 both studies), normalized area under the curve (AUC) of gastric H+ activity decreased (p < 0.05 study 2), and normalized AUC of esophageal H+ activity decreased (p < 0.05 both studies). The AUC of esophageal pH < 4 decreased. Normalized AUC of esophageal H+ activity decreased (p < 0.05 both studies), indicating refluxate pH increased, although this was not reflected in any change in mean esophageal pH or reflux index. The normalized AUC of esophageal H+ activity was a more sensitive measure of changes in esophageal pH.

Conclusions

In neonates, preterm infants, and infants aged 1 through 11 months, pantoprazole (high dose) improved pH-metry parameters after ≥5 consecutive daily doses, and was generally well tolerated for ≤6 weeks.

Keywords

Premature infant Newborn infant Infant Gastric acidity determination Gastroesophageal reflux Pharmacodynamics 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jaroslaw Kierkus
    • 1
  • Wanda Furmaga-Jablonska
    • 2
  • Janice E. Sullivan
    • 3
  • Elmer S. David
    • 4
  • Dan L. Stewart
    • 3
  • Natalie Rath
    • 5
  • Caifeng Fu
    • 5
  • Wenjin Wang
    • 5
  • Mary K. Maguire
    • 5
  • Gail M. Comer
    • 5
  1. 1.Department of Gastroenterology, Hepatology and ImmunologyThe Children’s Memorial Health InstituteWarsawPoland
  2. 2.Department of Neonates’ and Infants’ Pathology, Children’s University HospitalMedical University of LublinLublinPoland
  3. 3.Department of Pediatrics, Kosair Charities Pediatric Clinical Research Unit/Pediatric Pharmacology Research Unit (NICHD funded through grant U10 HD045934-05)University of LouisvilleLouisvilleUSA
  4. 4.UMDNJ-New Jersey Medical SchoolNewarkUSA
  5. 5.Pfizer Inc.CollegevilleUSA

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