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

Background Triptans, serotonin 5-HT 1B/1D receptor agonists, exert their action by targeting serotonin 5-HT 1B/1D receptors, are used for treatment of migraine attack. Presently, 5 different triptans, namely sumatriptan, zolmitriptan, eletriptan, rizatriptan, and naratriptan, are marketed in Japan....

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Bibliographic Details
Published in:Journal of headache and pain 2014-12, Vol.15 (1), p.85-11, Article 85
Main Authors: Tokuoka, Kentaro, Takayanagi, Risa, Suzuki, Yuji, Watanabe, Masayuki, Kitagawa, Yasuhisa, Yamada, Yasuhiko
Format: Article
Language:English
Subjects:
Headache
Humans
Internal Medicine
Medicine
Medicine & Public Health
Migraine
Migraine Disorders - drug therapy
Neurology
Oxazolidinones - pharmacokinetics
Oxazolidinones - therapeutic use
Pain Medicine
Pharmacodynamics
Piperidines - pharmacokinetics
Piperidines - therapeutic use
Pyrrolidines - pharmacokinetics
Pyrrolidines - therapeutic use
Research Article
Serotonin 5-HT1 Receptor Agonists - pharmacokinetics
Serotonin 5-HT1 Receptor Agonists - therapeutic use
Serotonin S1 receptors
Sumatriptan
Sumatriptan - pharmacokinetics
Sumatriptan - therapeutic use
Treatment Outcome
Triazoles - pharmacokinetics
Triazoles - therapeutic use
Tryptamines - pharmacokinetics
Tryptamines - therapeutic use
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Summary:Background Triptans, serotonin 5-HT 1B/1D receptor agonists, exert their action by targeting serotonin 5-HT 1B/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-HT 1B/1D receptor occupancy (Φ 1B and Φ 1D ). 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 (AUC cp ) and the areas under the time curves for Ф 1B and Ф 1D (AUC Ф 1B and AUC Ф 1D ). Moreover, parameters expressing drug transfer and binding rates ( A cp , A Ф 1B , A Ф 1D ) were calculated. Results Our calculations showed that Ф max 1B and Ф max 1D 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 AUC cp , AUC Φ 1B , AUC Φ 1D , and A cp  · AUC cp differed with each drug and administered form, whereas a significant relationship was found between the therapeutic effect and A Φ 1B  · AUC Φ 1B or A Φ 1D  · AUC Φ 1D 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.
ISSN:1129-2369
1129-2377
DOI:10.1186/1129-2377-15-85