title: Theoretical analysis of headache recurrence in patients administered triptans for migraine based on receptor occupancy.
abstract: BACKGROUND
  In this study, we retrospectively analyzed the relationship between headache recurrence and serotonin 5-HT1B/1D receptor occupancy (Φ1B and Φ1D). Triptans marketed in Japan (sumatriptan, zolmitriptan, eletriptan, rizatriptan, naratriptan) were investigated.
  
  
  METHODS
  Receptor occupancies were calculated from both the pharmacokinetic and pharmacodynamic data of triptans. We examined the relationships between recurrence rate and elimination half-lives, and Ф1B and Ф1D, as calculated from the time-course of plasma drug concentration obtained from other studies. The time until Ф1B and Ф1D became 50% or less, 40% or less, and 30% or less was calculated as duration time to examine the relationship with recurrence rate.
  
  
  RESULTS
  For Ф1B, eletriptan remained at a low level. For Ф1D, it was indicated that all triptans obtained an occupancy of 80% or higher at maximum. For all items, though recurrence tended to be lower along with longer half-life, no significant statistical correlation was found. For both Ф1B and Ф1D, the recurrence rate tended to be lower as the duration became longer. In addition, a significant correlation was observed for Ф1D (p < 0.05). For clarifying the Ф value and time period most closely correlated with recurrence rate, recurrence and Ф1B and Ф1D at 6, 12, and 18 h after administration were calculated. The most significant correlation was observed between recurrence rate and Ф1D at 12 h after administration (p < 0.01).
  
  
  CONCLUSIONS
  As an index for evaluating headache recurrence following triptan administration, recurrence rate and Ф1D value at 12 h after administration were found to be most closely correlated and useful for analysis. Our results indicate that headache recurrence inhibition can be evaluated using these values.
authors.affiliation: Department of Neurology, Tokai University Hachioji Hospital, 1838 Ishikawa-cho, Hachioji, Tokyo, 192-0032, Japan, tokuoka.kentaro@hachioji-hosp.tokai.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokuoka
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Mioko
authors.initials: M
authors.lastname: Toyabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D005260:Female; D006261:Headache / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D044302:Receptor, Serotonin, 5-HT1B / Q000097:blood*; D044346:Receptor, Serotonin, 5-HT1D / Q000097:blood*; D012008:Recurrence; D012189:Retrospective Studies; D017366:Serotonin Receptor Agonists / Q000097:blood* / Q000627:therapeutic use; D014363:Tryptamines / Q000097:blood* / Q000627:therapeutic use
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D017366:Serotonin Receptor Agonists; D014363:Tryptamines