Population pharmacodynamic modeling of various extended-release formulations of methylphenidate in children with attention deficit hyperactivity disorder via meta-analysis

  • Holly Kimko
  • Ekaterina Gibiansky
  • Leonid Gibiansky
  • H. Lynn Starr
  • Joris Berwaerts
  • Joseph Massarella
  • Frank Wiegand
Original Paper

Abstract

Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in children without conducting pediatric pharmacokinetic (PK) or PD studies by using more easily obtained adult PK data. Mean PK data from various extended-release MPH formulations studied in adults and mean PD data from nine pediatric efficacy studies were obtained from the literature. The individual time-course of the clinical measures from three pediatric trials were also analyzed after being combined with the meta-analysis data. The clinical measure profiles following placebo administration were described by indirect response models with time-varying elimination rates. MPH pharmacodynamic effect was described by Emax models, which included time-dependent tolerance. Internal and external evaluations using a visual predictive check technique confirmed the prediction capability of the models. This modeling exercise demonstrated that time courses of MPH concentrations in adults with different drug release patterns can be used to predict time courses of clinical efficacy parameters in pediatrics by employing the models developed by meta-analysis.

Keywords

Methylphenidate pharmacodynamics Attention deficit hyperactivity disorder Meta-analysis Population modeling Placebo model 

Supplementary material

10928_2011_9238_MOESM1_ESM.doc (148 kb)
Supplementary material 1 (DOC 147 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Holly Kimko
    • 1
  • Ekaterina Gibiansky
    • 2
  • Leonid Gibiansky
    • 2
  • H. Lynn Starr
    • 3
  • Joris Berwaerts
    • 4
  • Joseph Massarella
    • 5
  • Frank Wiegand
    • 6
  1. 1.Advanced Modeling & SimulationJanssen Research & Development, LLCRaritanUSA
  2. 2.QuantPharm, LLCNorth PotomacUSA
  3. 3.CNS Medical AffairsJanssen Scientific Affairs, LLCTitusvilleUSA
  4. 4.Neuroscience Therapeutic AreaJanssen Research & Development, LLCTitusvilleUSA
  5. 5.Clinical PharmacologyJanssen Research & Development, LLCRaritanUSA
  6. 6.Neurosciences Global Medical AffairsJanssen Global Services, LLCRaritanUSA

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