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Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan and naproxen sodium for the acute treatment of migraine.
- Source :
-
Headache [Headache] 2010 Mar; Vol. 50 (3), pp. 357-73. Date of Electronic Publication: 2010 Feb 02. - Publication Year :
- 2010
-
Abstract
- Objective: To describe the pharmacokinetic and safety profiles of sumatriptan 85 mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed-dose combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic dysmodulation and inflammation in migraine.<br />Methods: Six open-label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6).<br />Results: Consistently across studies, naproxen administered as a component of sumatriptan/naproxen sodium demonstrated a delayed-release profile similar to that of an enteric-coated product. Naproxen from the combination tablet showed a delayed time to peak plasma concentration and lower peak plasma concentration while exposures (area under the plasma concentration-time curve) were similar. The peak plasma concentration for naproxen was approximately 36% lower and the time to peak plasma concentration approximately 4 hours later when naproxen was administered as sumatriptan/naproxen sodium compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma concentration and area under the plasma concentration-time curve after administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were comparable to those after administration of a commercially available sumatriptan 100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on average, 30 minutes earlier with sumatriptan/naproxen sodium compared with sumatriptan 100 mg (RT). No clinically significant differences between sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified with respect to electrocardiograms, blood pressure, or heart rate. In addition, food had no significant effect on the bioavailability of naproxen or sumatriptan after administration of sumatriptan/naproxen sodium but slightly delayed the time to peak plasma concentration of sumatriptan by approximately 40 minutes. The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet. The adverse-event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose.<br />Conclusion: The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed-release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety of sumatriptan/naproxen sodium were observed.
- Subjects :
- Acute Disease therapy
Administration, Oral
Adult
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Anti-Inflammatory Agents, Non-Steroidal adverse effects
Biological Availability
Cross-Over Studies
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Combinations
Drug Compounding methods
Drug Synergism
Female
Humans
Inflammation drug therapy
Inflammation physiopathology
Male
Middle Aged
Migraine Disorders physiopathology
Naproxen adverse effects
Serotonin Receptor Agonists administration & dosage
Serotonin Receptor Agonists adverse effects
Serotonin Receptor Agonists pharmacokinetics
Sumatriptan adverse effects
Time Factors
Treatment Outcome
Migraine Disorders drug therapy
Naproxen administration & dosage
Naproxen pharmacokinetics
Sumatriptan administration & dosage
Sumatriptan pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1526-4610
- Volume :
- 50
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Headache
- Publication Type :
- Academic Journal
- Accession number :
- 20132340
- Full Text :
- https://doi.org/10.1111/j.1526-4610.2009.01606.x