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A pharmacokinetic interaction study of avitriptan and propranolol
P H Marathe1, D S Greene, G D Kollia
1Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Clinical Pharmacology and Therapeutics
|April 29, 1998
Summary
Coadministration of avitriptan and propranolol showed no clinically significant pharmacokinetic changes. Avitriptan can be safely used with propranolol for migraine treatment.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Drug Interactions
Background:
- Migraine is a common neurological disorder.
- Propranolol is a beta-blocker used for various conditions, including migraine prophylaxis.
- Avitriptan is a triptan medication used for acute migraine treatment.
Purpose of the Study:
- To evaluate potential pharmacokinetic interactions between avitriptan and propranolol.
- To determine if coadministration affects drug exposure and metabolism.
- To assess the safety of combining these medications for migraine therapy.
Main Methods:
- Healthy subjects received avitriptan and propranolol separately and concurrently.
- Pharmacokinetics of parent drugs and key metabolites were analyzed.
- Area under the plasma concentration-time curve (AUC) and peak concentrations were measured.
Main Results:
- No significant pharmacokinetic changes were observed for avitriptan.
- Propranolol AUC increased by 20%, while its metabolite 4-hydroxypropranolol AUC decreased.
- Avitriptan significantly increased exposure to its metabolites N-desmethylavitriptan and methoxypyrimidinyl piperazine by approximately 25%.
Conclusions:
- The observed increases in propranolol and avitriptan metabolite exposure are not clinically significant.
- Avitriptan can be safely coadministered with propranolol for abortive antimigraine therapy.
- This combination offers a potential treatment option for migraine patients on propranolol therapy.