Theory-based analysis of clinical efficacy of triptans using receptor occupancy

The Journal of Headache and Pain

Research Article

Kentaro Tokuoka¹  Yasuhisa Kitagawa¹  Yuji Suzuki²  Masayuki Watanabe²  Risa Takayanagi³  Yasuhiko Yamada³ 

[1] Department of Neurology, Tokai University Hachioji Hospital, 1838 Ishikawa-cho, Hachioji, 192-0032, Tokyo, Japan;Department of Pharmacy, Tokai University Hachioji Hospital, 1838 Ishikawa-cho, Hachioji, 192-0032, Tokyo, Japan;School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, 192-0392, Tokyo, Japan;

关键词: Triptans;    Serotonin 5-HT receptor agonists;    Receptor occupancy;    Migraine;   

DOI  :  10.1186/1129-2377-15-85

 received in 2014-09-17, accepted in 2014-11-20,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundTriptans, 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.MethodsTo 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.ResultsOur 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.ConclusionsThese 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.

【 授权许可】

Unknown   
© Tokuoka et al.; licensee Springer. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.