title: Relevance of absorption rate and lag time to the onset of action in migraine.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Maas
authors.forename: Marc A H
authors.initials: MA
authors.lastname: Spruit
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Della Pasqua
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption; D008390:Markov Chains; D008881:Migraine Disorders / Q000188:drug therapy*; D008954:Models, Biological; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012984:Software; D018170:Sumatriptan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan