title: Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation.
abstract: OBJECTIVE
  To quantitate onset of effect of all formulations of sumatriptan, and to investigate whether this is related to rate, not extent, of drug absorption.
  
  
  METHODS
  From published literature, for 4 formulations of sumatriptan and matching placebos, response rates were modeled using a simple logarithmic equation, with a being a parameter of curve convexity and B, a location parameter (equal to response rate at 2 hours [the standard regulatory parameter]). The average rate of drug absorption (A) was estimated by dividing the maximal drug concentration by the time needed to achieve it (Cmax/Tmax). Least mean square correlation was then performed between the therapeutic gains and therapeutic ratios of curve convexity and rate of drug absorption.
  
  
  RESULTS
  -Models closely fitted observed response rates (2 hours or less). Curve convexity correlated with rate of drug absorption. Sumatriptan response rates (0 to 2 hours) for formulations correlated with rate, not extent, of drug absorption. The range of rates of onset of effect among different routes of administration was greater than that for tablets with 4-fold differences in dose size.
  
  
  CONCLUSIONS
  Onset of effect is related to rate of absorption of sumatriptan. There is greater scope for improving onset of effect using an alternative route of administration than by increasing the oral dose.
authors.affiliation: EBD Group, Carlsbad, Calif 92009, USA.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Fox
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D008954:Models, Biological; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018170:Sumatriptan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D017366:Serotonin Receptor Agonists; D018170:Sumatriptan