Pharmacokinetics and tolerability of rabeprazole sodium in subjects aged 12 to 16 years with gastroesophageal reflux disease: an open-label, single- and multiple-dose study.

OBJECTIVE: This study was conducted to characterize the pharmacokinetic and safety profile of rabeprazole sodium tablets in children and adolescents with gastroesophageal reflux disease (GERD).

METHODS: This was a multicenter, open-label, single- and multiple-dose study in subjects aged 12 to 16 years with GERD. Subjects were stratified by age (12-<14 years and 14-16 years) and were randomized to receive oral rabeprazole 10 or 20 mg/d over 5 or 7 days (to accommodate weekends). The pharmacokinetic parameters calculated included C(max), T(max), AUC, t(1/2), and apparent oral clearance (day 5/7 only). Blood samples for pharmacokinetic determinations were obtained on study days 1, 2, and 5 (or 7) and at discharge on day 6 (or 8). Safety assessments, including adverse events (AEs), were performed at all study visits.

RESULTS: Twenty-four subjects were enrolled in the study (12 in each dose group); they were predominantly white, had a mean age of 14.2 years, and had a mean body mass index of 24.3 kg/m(2) (the 90th percentile for adolescents of this age in the United States). Mean age and weight did not differ significantly between the 2 dose groups. On day 1, C(max) was significantly greater in the rabeprazole 20-mg group compared with the rabeprazole 10-mg group (P = 0.024); on day 5/7, both AUC and C(max) were significantly greater in the rabeprazole 20-mg group compared with the rabeprazole 10-mg group (P = 0.005 and P = 0.007, respectively). Within-period comparisons for both groups indicated that the AUC and C(max) for rabeprazole and its thioether metabolite did not differ significantly from day 1 to day 5/7. In addition, the T(max) and t(1/2) were relatively unchanged from day 1 to day 5/7 in both dose groups. Treatment-emergent signs and symptoms occurred in 11 subjects, 6 in the 10-mg group and 5 in the 20-mg group. The most frequently reported AEs were headache and nausea (16.7% and 8.3%, respectively). No statistically significant differences were observed between dose groups in terms of the number of subjects with AEs.

CONCLUSIONS: Rabeprazole 10 and 20 mg were well tolerated in these children and adolescents with GERD. The results of the pharmacokinetic analyses of single and multiple oral doses indicated no apparent accumulation of rabeprazole or its thioether metabolite with the 10-mg dose. There was, however, a suggestion of accumulation with multiple dosing of rabeprazole 20 mg, which requires confirmation in larger studies.