Clinical Pharmacokinetics

, Volume 53, Issue 10, pp 943–957

Population Pharmacokinetics of Rabeprazole and Dosing Recommendations for the Treatment of Gastroesophageal Reflux Disease in Children Aged 1–11 Years

  • Sarah C. McLeay
  • Bruce Green
  • William Treem
  • An Thyssen
  • Erik Mannaert
  • Holly Kimko
Original Research Article

Abstract

Background and Objective

Rabeprazole sodium is a proton pump inhibitor used for the treatment of gastroesophageal reflux disease (GERD). The objective of this study was to develop a population pharmacokinetic model for rabeprazole that describes concentration–time data arising from phase I and phase III studies in adult and pediatric subjects, including neonates and preterm infants, and propose dosing recommendations for pediatric subjects aged 1–11 years.

Methods

A total of 4,417 pharmacokinetic observations from 597 subjects aged 6 days to 55.7 years with body weights of 1.15–100 kg were used to develop the population pharmacokinetic model using non-linear mixed-effects modeling techniques. Weight and age were included in the structural model to describe clearance (CL) and central volume of distribution (Vc). Other covariates considered during model development included sex, race, creatinine clearance, hepatic function, formulation, feeding status, and route of administration. The final model was used to determine doses for pediatric subjects aged 1–11 years to achieve a steady-state area under the plasma concentration–time curve across the dose interval of 24 h (AUC24) within the target adult AUC24 range obtained following a rabeprazole 10 mg dose.

Results

The best model was a two-compartment disposition model with a sequential zero-order duration of input (Dur), first-order absorption (ka) following a lag time (Tlag), with weight and age effects on CL and Vc. Formulation type and feeding status described some of the variability in bioavailability and the absorption parameters Tlag, Dur, and ka. A dosage regimen of 5 mg once daily for children <15 kg, and 10 mg for children ≥15 kg is recommended for 1- to 11-year-old pediatric patients with GERD.

Conclusions

The pharmacokinetics of rabeprazole were described with good precision following administration of rabeprazole across a range of doses and in a range of formulations.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Sarah C. McLeay
    • 1
  • Bruce Green
    • 1
  • William Treem
    • 2
  • An Thyssen
    • 3
  • Erik Mannaert
    • 3
  • Holly Kimko
    • 2
  1. 1.Model Answers Pty LtdBrisbaneAustralia
  2. 2.Janssen Research and Development, LLCRaritanUSA
  3. 3.Janssen Research and DevelopmentJanssen Pharmaceutica N.V.TurnhoutBelgium

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