A multicenter, randomized, open-label, pharmacokinetics and safety study of pantoprazole tablets in children and adolescents aged 6 through 16 years with gastroesophageal reflux disease

Abstract

Children with gastroesophageal reflux disease (GERD) may benefit from gastric acid suppression with proton pump inhibitors such as pantoprazole. Effective treatment with pantoprazole requires correct dosing and understanding of the drug's kinetic profile in children. The aim of these studies was to characterize the pharmacokinetic (PK) profile of single and multiple doses of pantoprazole delayed-release tablets in pediatric patients with GERD aged 6 to 11 years (study 1) and 12 to 16 years (study 2). Patients were randomly assigned to receive pantoprazole 20 or 40 mg once daily. Plasma pantoprazole concentrations were obtained at intervals through 12 hours after the single dose and at 2 and 4 hours after multiple doses for PK evaluation. PK parameters were derived by standard noncompartmental methods and examined as a function of both drug dose and patient age. Safety was also monitored. Pantoprazole PK was dose independent (when dose normalized) and similar to PK reported from adult studies. There was no evidence of accumulation with multiple dosing or reports of serious drug-associated adverse events. In children aged 6 to 16 years with GERD, currently available pantoprazole delayed-release tablets can be used to provide systemic exposure similar to that in adults.

Figure 1

Plasma concentration-time profiles after a single dose of pantoprazole tablet in (A) children aged 6 through 11 years (study 1) and (B) adolescents aged 12 through 16 years (study 2).

Figure 1

Plasma concentration-time profiles after a single dose of pantoprazole tablet in (A) children aged 6 through 11 years (study 1) and (B) adolescents aged 12 through 16 years (study 2).

Figure 2

Individual and mean AUC values after a single dose of pantoprazole tablet in (A) children aged 6 through 11 years (study 1) and (B) adolescents aged 12 through 16 years (study 2).

Figure 3

Mean (SE) plasma concentration-time profiles after single and multiple doses of pantoprazole tablet 20 mg and 40 mg in (A) children aged 6 through 11 years (study 1) and (B) adolescents aged 12 through 16 years (study 2).

Figure 3

Mean (SE) plasma concentration-time profiles after single and multiple doses of pantoprazole tablet 20 mg and 40 mg in (A) children aged 6 through 11 years (study 1) and (B) adolescents aged 12 through 16 years (study 2).

Figure 4

Individual values for clearance (CL/F) versus age after a single dose of pantoprazole tablet in patients aged 6 through 16 years (studies 1 and 2 combined).

Figure 5

Box plot of pantoprazole area under the curve (AUC) normalized for dose versus CYP2C19 genotype in pediatric patients (studies 1 and 2 combined).