Pharmacodynamics and safety of pantoprazole in neonates, preterm infants, and infants aged 1 through 11 months with a clinical diagnosis of gastroesophageal reflux disease.

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.