caa a22 4500 445797428 CHVBK 20180317145130.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10620-010-1321-3 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1321-3 Pharmacodynamics and Safety of Pantoprazole in Neonates, Preterm Infants, and Infants Aged 1 Through 11 Months with a Clinical Diagnosis of Gastroesophageal Reflux Disease [Elektronische Daten] [Jaroslaw Kierkus, Wanda Furmaga-Jablonska, Janice Sullivan, Elmer David, Dan Stewart, Natalie Rath, Caifeng Fu, Wenjin Wang, Mary Maguire, Gail Comer] 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, ~1.2mg/kg [high dose]) and infants 1 through 11months (study 2, ~0.6 [low dose] or ~1.2mg/kg [high dose]) received once-daily pantoprazole. Twenty-four-hour dual-electrode pH-metry parameters were compared between predose and steady state (≥5days) (two-sided paired t test). Treatment was administered for ≤6weeks. 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 11months, pantoprazole (high dose) improved pH-metry parameters after ≥5 consecutive daily doses, and was generally well tolerated for ≤6weeks. Springer Science+Business Media, LLC, 2010 Premature infant nationallicence Newborn infant nationallicence Infant nationallicence Gastric acidity determination nationallicence Gastroesophageal reflux nationallicence Pharmacodynamics nationallicence Kierkus Jaroslaw Department of Gastroenterology, Hepatology and Immunology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland aut Furmaga-Jablonska Wanda Department of Neonates' and Infants' Pathology, Children's University Hospital, Medical University of Lublin, Lublin, Poland aut Sullivan Janice Department of Pediatrics, Kosair Charities Pediatric Clinical Research Unit/Pediatric Pharmacology Research Unit (NICHD funded through grant U10 HD045934-05), University of Louisville, KCPCRU, 231 E. Chestnut, N-97, 40202, Louisville, KY, USA aut David Elmer UMDNJ-New Jersey Medical School, Newark, NJ, USA aut Stewart Dan Department of Pediatrics, Kosair Charities Pediatric Clinical Research Unit/Pediatric Pharmacology Research Unit (NICHD funded through grant U10 HD045934-05), University of Louisville, KCPCRU, 231 E. Chestnut, N-97, 40202, Louisville, KY, USA aut Rath Natalie Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut Fu Caifeng Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut Wang Wenjin Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut Maguire Mary Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut Comer Gail Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 425-434 0163-2116 56:2<425 2011 56 10620 https://doi.org/10.1007/s10620-010-1321-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1321-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kierkus Jaroslaw Department of Gastroenterology, Hepatology and Immunology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland aut NATIONALLICENCE 700 1- Furmaga-Jablonska Wanda Department of Neonates' and Infants' Pathology, Children's University Hospital, Medical University of Lublin, Lublin, Poland aut NATIONALLICENCE 700 1- Sullivan Janice Department of Pediatrics, Kosair Charities Pediatric Clinical Research Unit/Pediatric Pharmacology Research Unit (NICHD funded through grant U10 HD045934-05), University of Louisville, KCPCRU, 231 E. Chestnut, N-97, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- David Elmer UMDNJ-New Jersey Medical School, Newark, NJ, USA aut NATIONALLICENCE 700 1- Stewart Dan Department of Pediatrics, Kosair Charities Pediatric Clinical Research Unit/Pediatric Pharmacology Research Unit (NICHD funded through grant U10 HD045934-05), University of Louisville, KCPCRU, 231 E. Chestnut, N-97, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Rath Natalie Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut NATIONALLICENCE 700 1- Fu Caifeng Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut NATIONALLICENCE 700 1- Wang Wenjin Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut NATIONALLICENCE 700 1- Maguire Mary Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut NATIONALLICENCE 700 1- Comer Gail Pfizer Inc., 500 Arcola Road, 19426, Collegeville, PA, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 425-434 0163-2116 56:2<425 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer