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Pharmacokinetics and Tolerability of Rabeprazole in Children 1 to 11 Years Old With Gastroesophageal Reflux Disease

Zannikos, Peter N*; Doose, Dennis R*; Leitz, Gerhard J*; Rusch, Sarah; Gonzalez, Martha D*; Solanki, Bhavna*; Haddad, Ibrahim; Mulberg, Andrew E*

Journal of Pediatric Gastroenterology and Nutrition: June 2011 - Volume 52 - Issue 6 - p 691–701
doi: 10.1097/MPG.0b013e318207834d
Original Articles: Gastroenterology

Background: The pharmacokinetics of rabeprazole after a single oral dose and once-daily administration for 5 consecutive days was characterized in children 1 to 11 years old with gastroesophageal reflux disease (GERD).

Patients and Methods: The initial 8 patients received rabeprazole sodium (hereafter referred to as rabeprazole) 0.14 mg/kg (part 1); the next 20 patients were randomized to receive 0.5 or 1 mg/kg (part 2) to target concentrations in plasma expected to be safe and effective. Pharmacokinetic parameters of rabeprazole and the thioether metabolite were calculated using noncompartmental methods. Subjective evaluations of GERD severity, rabeprazole short-term effectiveness, palatability, and safety were also characterized.

Results: Rabeprazole concentrations increased in a dose-dependent manner. Little or no accumulation was observed after repeated administration. The results suggest that formation of the thioether is an important metabolic pathway in young patients, which is consistent with adults. Plasma area under the concentration-time curve values of rabeprazole and the metabolite were poorly correlated with individual age and body weight. Furthermore, oral rabeprazole clearance values (not adjusted for weight) were similar to historical adult data. However, weight-adjusted values were higher for the pediatric patients, and approximately 2 to 3 times the milligram per kilogram dose of rabeprazole in these children was necessary to achieve comparable concentrations in adults. Subjective evaluations demonstrated an improvement of GERD symptoms in most patients after rabeprazole treatment.

Conclusions: Palatability of the formulation was reported to be good or excellent. Rabeprazole was well tolerated, with no notable differences in safety among the dose groups.

*Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ

Beerse, Belgium

Youngstown, OH.

Received 3 June, 2010

Accepted 17 October, 2010

Address correspondence and reprint requests to Peter N. Zannikos, Office No. K30704, 1125 Trenton-Harbourton Rd, Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ, 08560 (e-mail:

The present study was sponsored by Johnson & Johnson Pharmaceutical Research and Development, LLC, and Eisai Medical Research, Inc.

The authors are employees of Johnson & Johnson.

Copyright 2011 by ESPGHAN and NASPGHAN