Pharmacokinetic properties of esomeprazole in children aged 1 to 11 years with symptoms of gastroesophageal reflux disease: A randomized, open-label study

The aim of this study was to assess the overall exposure, other pharmacokinetic (PK) properties, and tolerability of esomeprazole magnesium after repeated oral doses of 5, 10, and 20 mg in pediatric patients who had symptoms of gastroesophageal reflux disease (GERD). This randomized, open-label study was conducted at West Coast Clinical Trials, Long Beach, California. Boys and girls aged 1 to 11 years who had a clinical diagnosis of GERD were included and stratified by age (1–5 years [younger group] and 6–11 years [older group]). For this 5-day study, children in the younger group were randomly assigned to receive 1 esomeprazole 5- or 10-mg capsule PO QD, and those in the older group were randomly assigned to receive 1 esomeprazole 10- or 20-mg capsule PO QD. On days 1 to 4, study medications were administered with the supervision of the study personnel 1 hour before breakfast. Blood samples were collected within 0.5 hour before and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours after study drug administration on day 5. Plasma concentrations of esomeprazole were measured using reverse-phase liquid chromatography and mass-spectrometric detection. Tolerability assessments were performed by reviewing the number and severity of adverse events (collected via spontaneous reporting and direct questioning) and findings from the physical examination, which included vital-sign measurements and laboratory analysis (hematology, biochemistry, and urinalysis). Site personnel supervised the administration of the study drug to ensure compliance with treatment. The study included 31 children (17 boys, 14 girls; mean age, 5 years; 18 children in the younger group, 13 in the older group). A total of 27 children were included in the PK analysis. In the younger group, the geometric mean AUC 0−∞ and C max values in the esomeprazole 10-mg group were >2-fold that in the 5-mg group (AUC 0−∞, 4.83 and 0.74 pmol · h/L [0.32 and 0.04 μmol · h · L −1/kg], respectively; C max, 2.98 and 0.62 μmol/L [0.19 and 0.03 μmol/L · kg −1], respectively). In the older group, the geometric mean AUC 0−∞ and C max values for the 20-mg dose group were ∼2-fold those for the 10-mg dose group (AUC 0−∞, 6.28 and 3.70 μmol · h/L [0.21 and 0.12 pmol · h · L −1/kg], respectively; C max, 3.73 and 1.77 μmol/L [0.13 and 0.06 μmol/L · kg 1], respectively). For the 10-mg esomeprazole dose, the geometric mean body-weight-normalized apparent oral clearance was ∼50% higher in the younger group compared with the older group (0