PHARMACOKINETICS OF MULTIPLE DOSES OF ESOMEPRAZOLE IN PEDIATRIC PATIENTS AGED 1 TO 11 YEARS WITH SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE

Abstract

Purpose: To determine the pharmacokinetics (PK) of esomeprazole after repeated oral doses in pediatric patients with gastroesophageal reflux disease (GERD) symptoms. Methods: In this single-center, open-label study (D9614C00099), children aged 1-5 years inclusive received esomeprazole 5 or 10 mg, and children aged 6-11 years inclusive received esomeprazole 10 or 20 mg once daily for 5 days. Plasma esomeprazole was measured using normal-phase liquid chromatography and UV detection in blood samples taken <30 minutes before and 0.5, 1, 1.5, 2, 3, 4, and 6 hours after dosing on day 5 (presumed steady state). Results: Of these children, 55% were boys. In the younger children, AUC and Cmax with the 10-mg dose were more than twice that with the 5-mg dose, and t1/2λz was nearly twice that observed with the 5-mg dose. In the older children, AUC and Cmax with the 20-mg dose were approximately twice that with the 10-mg dose; t1/2λz and tmax were comparable. With the 10-mg dose, t1/2λz was similar in both age groups. The mean apparent clearance (Cl/F) adjusted for body weight was >50% higher in 1-5-year-old than in the older children. All doses were well tolerated; 2 mild adverse events were reported. Conclusions: The difference between the lower and higher doses in overall exposure (AUC) was greater in the younger than in the older children. Comparison of the 10-mg dose of esomeprazole in the 2 age groups suggests that 1-5-year-old children metabolize esomeprazole more rapidly per body weight than 6-11-year-old children.Table 1