Clinical Pharmacokinetics

, Volume 57, Issue 11, pp 1473–1475 | Cite as

Authors’ Reply to Standing et al.: “Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials”

  • Sven C. van Dijkman
  • Nico C. B. de Jager
  • Willem M. Rauwé
  • Meindert Danhof
  • Oscar Della PasquaEmail author
Letter to the Editor
In their comments on our recent paper, Standing et al. [ 1] raise questions about the plausibility of the (de)maturation function used to describe differences in the clearance of lamotrigine, where patients younger than 2 years of age show, on average, a higher clearance than adults after correction for body weight. The authors discuss three possible scenarios that could lead to model misspecification. Whilst their arguments highlight important points to consider during model development and evaluation, we contest these points on a case-by-case basis and provide additional evidence for the increase in clearance and proposed (de)maturation function.
  1. 1.

    The inclusion of elderly subjects does not lead to biasAlthough we acknowledge that the step function used to describe changes in the apparent total clearance of the drug from plasma after oral administration (CL/F) in patients > 65 years of age is arbitrary (i.e. the cut-off age was not estimated), the available pharmacokinetic data...



No external funding was used in the preparation of this reply.

Compliance with Ethical Standards

Conflict of interest

Oscar Della Pasqua is Senior Director Clinical Pharmacology at GlaxoSmithKline and owns GlaxoSmithKline shares. Sven C. van Dijkman, Nico C.B. de Jager, Willem M. Rauwé, and Meindert Danhof have no conflicts of interest directly relevant to the contents of this reply.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sven C. van Dijkman
    • 1
  • Nico C. B. de Jager
    • 1
  • Willem M. Rauwé
    • 1
  • Meindert Danhof
    • 1
  • Oscar Della Pasqua
    • 2
    • 3
    Email author
  1. 1.Division of PharmacologyLACDRLeidenThe Netherlands
  2. 2.Clinical Pharmacology Modelling and SimulationGlaxoSmithKlineUxbridgeUK
  3. 3.Clinical Pharmacology and Therapeutics GroupUCLLondonUK

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