Pharmacokinetics and acid-suppressive effects of esomeprazole in infants 1-24 months old with symptoms of gastroesophageal reflux disease

Objectives: To evaluate the pharmacokinetics and acid-suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD). Patients and Methods: In this single-blind, randomized, parallel-group study, 50 infants 1 to 24 months old with symptoms of GERD, and ≥5% of time with intraesophageal pH <4 during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n=26) or 1 mg/kg (n=24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis. Results: At baseline, mean percentages of time with intragastric pH >4 and intraesophageal pH <4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25mg/kg group and 28.6% and 12.5% in the esomeprazole 1mg/kg group. After 1 week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the esomeprazole 0.25mg/kg and 1mg/kg groups, respectively (P<0.001 vs baseline), and times with intraesophageal pH <4 were 8.4% (P<0.05 vs baseline) and 5.5% (P<0.001 vs. baseline), respectively. The mean number of acid reflux episodes of > 5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25mg/kg and 1mg/kg, respectively. The geometric mean AUC_0-t of esomeprazole were 0.24 and 1.79 μmmol·h/L for the 0.25mg/kg and 1mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated. Conclusions: Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.