Theoretical analysis of headache recurrence in patients administered triptans for migraine based on receptor occupancy

BACKGROUND: In this study, we retrospectively analyzed the relationship between headache recurrence and serotonin 5-HT(1B/1D) receptor occupancy (Φ(1B) and Φ(1D)). 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 Ф(1B) and Ф(1D), as calculated from the time-course of plasma drug concentration obtained from other studies. The time until Ф(1B) and Ф(1D) 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 Ф(1B), eletriptan remained at a low level. For Ф(1D), 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 Ф(1B) and Ф(1D), the recurrence rate tended to be lower as the duration became longer. In addition, a significant correlation was observed for Ф(1D) (p < 0.05). For clarifying the Ф value and time period most closely correlated with recurrence rate, recurrence and Ф(1B) and Ф(1D) at 6, 12, and 18 h after administration were calculated. The most significant correlation was observed between recurrence rate and Ф(1D) at 12 h after administration (p < 0.01). CONCLUSIONS: As an index for evaluating headache recurrence following triptan administration, recurrence rate and Ф(1D) 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.