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.
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Notes
Preterm infants were defined as infants who were born before 37 completed weeks of gestation. Neonates were defined as term or postterm infants in the first 28 days since birth. Term infants were defined as those born after 37–42 weeks of gestation, and postterm infants were defined as those born after 42 weeks of gestation. Gestational age was the estimated number of weeks between the first day of the mother’s last menstrual period and the day of delivery. Postnatal age was the age since birth in weeks. Corrected age in study 1, also referred to in the literature as postmenstrual age, was the sum of gestational age and the age since birth in weeks.
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Acknowledgments
These studies were sponsored by Wyeth Research, which was acquired by Pfizer Inc. in October 2009. The authors thank Tuli Ahmed for providing professional medical writing assistance funded by Wyeth Research. The following investigators participated in the PD portion of study 1: Tracie L. Miller, University of Miami, Miller School of Medicine, Miami, FL, USA; Mark J. Polak, West Virginia University School of Medicine, Department of Pediatrics, Morgantown, WV, USA; Dan L. Stewart, Kosair Charities Pediatric Clinical Research Unit and Pediatric Pharmacology Research Unit (NICHD 1 U10 HD 0495934-04), University of Louisville, Louisville, KY, USA; Manoj C. Shah, Loma Linda University, Department of Pediatrics, Loma Linda, CA, USA; Elmer David, University of Medicine & Dentistry of NJ, New Jersey Medical School, Newark, NJ, USA; Wanda Furmaga-Jablonska, Department of Neonates’ and Infants’ Pathology, Children’s University Hospital, Medical University of Lublin, Lublin, Poland; Piotr Korbal, Oddzial Noworodkow i Wczesniakow z Intensywna Terapia Noworodka, SP ZOZ Wojewodzki Szpital im. Dr J. Biziela, Bydgoszcz, Poland; Christophe Dupont, Hôpital Saint Vincent de Paul, Service de Médecine Néonatale, Paris, France; Bart van Overmeire, University Hospital Antwerp, Department of Neonatology, Edegem, Belgium; and Salvatore Cucchiara, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy. The following investigators participated in the PD portion of study 2: Janice E. Sullivan, Kosair Charities Pediatric Clinical Research Unit and Pediatric Pharmacology Research Unit (NICHD 1 U10 HD 0495934-04), University of Louisville, Louisville, KY, USA; Steven Lobritto, Columbia University Medical Center, Division of Pediatric Gastroenterology, Hepatology & Nutrition, New York, NY, USA; Jaroslaw Kierkus, Department of Gastroenterology, Hepatology and Immunology, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland; Wanda Furmaga-Jablonska, Department of Neonates’ and Infants’ Pathology, Children’s University Hospital, Medical University of Lublin, Lublin, Poland; Christophe Dupont, Hôpital Saint Vincent de Paul, Service de Médecine Néonatale, Paris, France; Burkhard Rodeck, Marienhospital, Klinik fuer Kinderheilkunde und Jugendmedizin, Osnabrueck, Germany; Alberto Ravelli, Gastrointestinal Pathophysiology and Endoscopy, University Department of Pediatrics, Children’s Hospital, Spedali Civili, Brescia, Italy; Annamaria Staiano, Dipartimento di Pediatria, Università di Napoli, “Federico II,” Napoli, Italy; Peter Lewindon, Department of Gastroenterology, Royal Children’s Hospital, Herston, Queensland, Australia; and Etienne Sokal, Université Catholique de Louvain, Cliniques St. Luc, Brussels, Belgium.
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Kierkus, J., Furmaga-Jablonska, W., Sullivan, J.E. et al. Pharmacodynamics and Safety of Pantoprazole in Neonates, Preterm Infants, and Infants Aged 1 Through 11 Months with a Clinical Diagnosis of Gastroesophageal Reflux Disease. Dig Dis Sci 56, 425–434 (2011). https://doi.org/10.1007/s10620-010-1321-3
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DOI: https://doi.org/10.1007/s10620-010-1321-3