Pharmacokinetics of Two Dose Levels of Pantoprazole Sodium Delayed-Release Granules for Oral Suspension in Infants Aged 1 Through 11 Months with a Presumed Diagnosis of GERD: 1346

Purpose: Characterize the pharmacokinetic (PK) profile of single and repeated oral doses of pantoprazole at baseline and at steady state in infants aged 1 through 11 months with presumed GERD. Methods: This was a multicenter, open-label, randomized study. Pantoprazole was administered once daily for a minimum of 5 consecutive days. Patients were randomly assigned to either a high (1.2 mg/kg) or low (0.6 mg/kg) dose group, and the actual dose was based on their baseline weight. Plasma concentrations were determined by LC/MS/MS from samples obtained pre-dose and 0.5, 1, 2, 4, 6 and 12 hours post dose on study day 1, and at 2 and 4 hours post dose after 5 consecutive daily doses (steady state). The concentration-time data were analyzed using non-compartmental methods. Mean (SD) PK parameters, summarized by dose group, included peak concentration (Cmax), time to Cmax (tmax), area under the concentration-time curve (AUC), half-life (t1/2), and apparent clearance (Cl/F). Routine safety was evaluated by adverse events (AEs), physical examinations, vital signs, ECGs and laboratory tests. Genotyping was done for CYP2C19 and CYP3A4. Results: 27 males and 15 females with a mean age/corrected age of 5.45 months (range 1.1–11.9 months) completed the PK component of the study. The race/ethnicity distribution was 64% Caucasian, 33% Black and 2% Other. Twenty-three were full term infants. There were no poor metabolizers for CYP2C19. Seven patients were heterozygous for CYP2C19*1/*2 and 8 for CYP3A4*1/*1B, and 3 were homozygous for CYP3A4*1B/*1B. The PK parameters are presented in the table below. There was no evidence of drug accumulation upon multiple dosing. There was one serious AE and it was deemed unrelated to pantoprazole (in the low dose group). Few treatment-related AEs occurred. Conclusion: The pharmacokinetics of pantoprazole in children ages 1 through 11 months with GERD was well characterized and exposures with the 1.2 mg/kg dose were similar to that of adults receiving 40 mg tablet. The doses used in this study were safe and well tolerated.Table