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.
RCT Entities:
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.
Authors: Sarah C McLeay; Bruce Green; William Treem; An Thyssen; Erik Mannaert; Holly Kimko Journal: Clin Pharmacokinet Date: 2014-10 Impact factor: 6.447