Clinical Pharmacokinetics

, Volume 47, Issue 2, pp 139–146 | Cite as

Relevance of Absorption Rate and Lag Time to the Onset of Action in Migraine

  • Hugo J. Maas
  • Marc A. H. Spruit
  • Meindert Danhof
  • Oscar E. Della Pasqua
Original Research Article

Abstract

Objective: The objective of this analysis was to simulate the performance of oral triptan formulations with varying absorption characteristics and their impact on the onset and magnitude of the antimigraine effect using a Markov model for migraine attacks.

Analysis: Sumatriptan pharmacokinetic data were obtained from clinical pharmacology studies in which marketed solid formulations were administered. Based on a population pharmacokinetic model, mean concentration-time profiles were generated by varying the absorption rate constant and lag time. Subsequently, the simulated profiles were evaluated in a disease model of migraine to predict the onset and duration of the effect (the pain-free, pain-relief response).

Results: Based on a therapeutic dose of 50 mg of sumatriptan, a maximum gain in the pain-free response of 12% was achieved with an increased absorption rate. This gain in the response was reached approximately 0.5 hours after administration. A decrease only in the lag time with respect to the currently available formulations (i.e. 0.24 hours) resulted in a maximum gain of 5% in the pain-free response, which in contrast may not be interpreted as clinically relevant.

Conclusion: Model-based predictions suggest that increases in the absorption rate of the currently marketed oral formulation of sumatriptan result in a gain in the pain-free response that is both clinically and statistically relevant.

Notes

Acknowledgements

This manuscript is part of a PhD research fellowship programme sponsored by GlaxoSmithKline, UK. GlaxoSmithKline had no further role in the research rationale, collection, analysis and interpretation of the data in the final contents of the manuscript submitted for publication. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Hugo J. Maas
    • 1
  • Marc A. H. Spruit
    • 1
  • Meindert Danhof
    • 1
  • Oscar E. Della Pasqua
    • 1
    • 2
  1. 1.Leiden/Amsterdam Center for Drug ResearchLeiden UniversityLeidenThe Netherlands
  2. 2.Clinical Pharmacology & Discovery MedicineGlaxoSmithKlineGreenfordUK

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