Abstract
BackgroundIn 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.MethodsReceptor 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.ResultsFor 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).ConclusionsAs 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.
Highlights
In this study, we retrospectively analyzed the relationship between headache recurrence and serotonin 5-HT1B/1D receptor occupancy (Φ1B and Φ1D)
Concerning headache recurrence following triptan administration, relationships between recurrence and elimination half-lives of plasma drug concentrations have been reported in other countries [2], whereas nearly nothing has been presented on this subject in Japan
Our department performed analysis of the clinical effects of triptans by focusing on serotonin 5-HT1B and 5-HT1D receptor occupancies (Ф), and we found that the parameter
Summary
We retrospectively analyzed the relationship between headache recurrence and serotonin 5-HT1B/1D receptor occupancy (Φ1B and Φ1D). Concerning headache recurrence following triptan administration, relationships between recurrence and elimination half-lives of plasma drug concentrations have been reported in other countries [2], whereas nearly nothing has been presented on this subject in Japan. Our department performed analysis of the clinical effects of triptans (headache relief rate) by focusing on serotonin 5-HT1B and 5-HT1D receptor occupancies (Ф), and we found that the parameter (AФ AUCФ) of the area under the time curve of Ф (AUCФ) until the efficacy evaluation time point after correction by the velocity factor AФ (Фmax/Tmax) could serve as an index to correct the differences between drug and formulations, and uniformly evaluate them [3, 4]. We performed a theoretical evaluation of headache recurrence following triptan administration in Japanese based on serotonin 5-HT1B and 5-HT1D receptor occupancies
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