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

Tokuoka K, Takayanagi R, Toyabe M, Watanabe M, Kitagawa Y, Yamada Y - J Headache Pain (2015)

Bottom Line: For all items, though recurrence tended to be lower along with longer half-life, no significant statistical correlation was found.In addition, a significant correlation was observed for Ф1D (p < 0.05).The most significant correlation was observed between recurrence rate and Ф1D at 12 h after administration (p < 0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Tokai University Hachioji Hospital, 1838 Ishikawa-cho, Hachioji, Tokyo, 192-0032, Japan, tokuoka.kentaro@hachioji-hosp.tokai.ac.jp.

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.

No MeSH data available.


Related in: MedlinePlus

Changes in Ф1B and Ф1D at the time of usual-dose administration. (SC: subcutaneous injection, Tab: oral tablet, solid line: usual-dose in Japan)
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Fig2: Changes in Ф1B and Ф1D at the time of usual-dose administration. (SC: subcutaneous injection, Tab: oral tablet, solid line: usual-dose in Japan)

Mentions: Changes in plasma drug concentrations after a single-dose administration for 5 triptans in Japanese subjects are shown in Fig. 1. These data included not only usual but also clinical dose data by which evaluation of recurrence rate was reported. Changes in serotonin 5-HT1B and 5-HT1D receptor occupancies (Ф1B and Ф1D) at the time of usual-dose administration calculated from the pharmacokinetic and pharmacodynamic parameters are shown in Fig. 2.Fig. 1


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

Tokuoka K, Takayanagi R, Toyabe M, Watanabe M, Kitagawa Y, Yamada Y - J Headache Pain (2015)

Changes in Ф1B and Ф1D at the time of usual-dose administration. (SC: subcutaneous injection, Tab: oral tablet, solid line: usual-dose in Japan)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524853&req=5

Fig2: Changes in Ф1B and Ф1D at the time of usual-dose administration. (SC: subcutaneous injection, Tab: oral tablet, solid line: usual-dose in Japan)
Mentions: Changes in plasma drug concentrations after a single-dose administration for 5 triptans in Japanese subjects are shown in Fig. 1. These data included not only usual but also clinical dose data by which evaluation of recurrence rate was reported. Changes in serotonin 5-HT1B and 5-HT1D receptor occupancies (Ф1B and Ф1D) at the time of usual-dose administration calculated from the pharmacokinetic and pharmacodynamic parameters are shown in Fig. 2.Fig. 1

Bottom Line: For all items, though recurrence tended to be lower along with longer half-life, no significant statistical correlation was found.In addition, a significant correlation was observed for Ф1D (p < 0.05).The most significant correlation was observed between recurrence rate and Ф1D at 12 h after administration (p < 0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Tokai University Hachioji Hospital, 1838 Ishikawa-cho, Hachioji, Tokyo, 192-0032, Japan, tokuoka.kentaro@hachioji-hosp.tokai.ac.jp.

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.

No MeSH data available.


Related in: MedlinePlus