Pharmacodynamics and safety of pantoprazole in neonates, preterm infants, and infants aged 1 through 11 months with a clinical diagnosis of gastroesophageal reflux disease.
BACKGROUND
Limited data on proton pump inhibitors in infants led regulatory agencies to request sponsors to conduct pediatric studies.


OBJECTIVE
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.
Kierkus
Jaroslaw
J
Department of Gastroenterology, Hepatology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland. j.kierkus@med-net.pl
Furmaga-Jablonska
Wanda
W
Sullivan
Janice E
JE
David
Elmer S
ES
Stewart
Dan L
DL
Rath
Natalie
N
Fu
Caifeng
C
Wang
Wenjin
W
Maguire
Mary K
MK
Comer
Gail M
GM
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D000077402:Pantoprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole