title: Theory-based analysis of clinical efficacy of triptans using receptor occupancy.
abstract: BACKGROUND
  Triptans, serotonin 5-HT1B/1D receptor agonists, exert their action by targeting serotonin 5-HT1B/1D receptors, are used for treatment of migraine attack. Presently, 5 different triptans, namely sumatriptan, zolmitriptan, eletriptan, rizatriptan, and naratriptan, are marketed in Japan. In the present study, we retrospectively analyzed the relationships of clinical efficacy (headache relief) in Japanese and 5-HT1B/1D receptor occupancy (Φ1B and Φ1D). Receptor occupancies were calculated from both the pharmacokinetic and pharmacodynamic data of triptans.
  
  
  METHODS
  To evaluate the total amount of exposure to drug, we calculated the area under the plasma concentration-time curve (AUCcp) and the areas under the time curves for Ф1B and Ф1D (AUCФ1B and AUCФ1D). Moreover, parameters expressing drug transfer and binding rates (Acp, AФ1B, AФ1D) were calculated.
  
  
  RESULTS
  Our calculations showed that Фmax1B and Фmax1D were relatively high at 32.0-89.4% and 68.4-96.2%, respectively, suggesting that it is likely that a high occupancy is necessary to attain the clinical effect. In addition, the relationships between therapeutic effect and AUCcp, AUCΦ1B, AUCΦ1D, and Acp · AUCcp differed with each drug and administered form, whereas a significant relationship was found between the therapeutic effect and AΦ1B · AUCΦ1B or AΦ1D · AUCΦ1D that was not affected by the drug and the form of administration.
  
  
  CONCLUSIONS
  These results suggest that receptor occupancy can be used as a parameter for a common index to evaluate the therapeutic effect. We considered that the present findings provide useful information to support the proper use of triptans.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokuoka
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. yamada@ps.toyaku.ac.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000627:therapeutic use; D010880:Piperidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D058825:Serotonin 5-HT1 Receptor Agonists / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018170:Sumatriptan / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D014363:Tryptamines / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D023303:Oxazolidinones; D010880:Piperidines; D011759:Pyrrolidines; D058825:Serotonin 5-HT1 Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C115647:eletriptan; C089750:zolmitriptan; C093622:rizatriptan; D018170:Sumatriptan; C106783:naratriptan