Effect of subcutaneous naratriptan on forearm blood flow.
This randomized, double-blind, placebo-controlled, four-way crossover study was conducted on an in-clinic basis to assess forearm perfusion after subcutaneous (s.c.) naratriptan and placebo by reserve volume (hyperemic/baseline) and basal forearm blood flow (FBF) measured by strain gauge plethysmography. Nineteen male and female volunteer migraine subjects (International Headache Society criteria) received s.c. naratriptan 1 mg, 5 mg, 10 mg, and placebo on four separate study days outside a migraine attack. FBF was recorded at baseline, at 7-min intervals post-dose up to 1 h (basal) and once after sublingual glyceryl trinitrate administered at 1 h (hyperemic). Vital signs and electrocardiograms were recorded at baseline and 15, 30, 45, and 60 min post-dose. There were no statistically significant differences in reserve volume (hyperemic/baseline) between any dose of s.c. naratriptan and placebo. The naratriptan to placebo ratio was 102% (95% CI: 87-120%; p = 0.789) for 1 mg; 97% (95% CI: 83-114%, p = 0.737) for 5 mg; and 92% (95% CI: 79-108%; p = 0.325) for 10 mg. There were no statistically significant differences in basal FBF for any dose compared to placebo. The naratriptan to placebo ratio was 95% (95% CI: 87-104%; p = 0.263) for 1 mg; 94% (95% CI: 86-102%; p = 0.142) for 5 mg; and 94% (95% CI: 86-103%; p = 0.157) for 10 mg. The percentage of patients reporting adverse events was 53% with placebo, 53% with s.c. naratriptan 1 mg, 89% with 5 mg and 89% with 10 mg. In conclusion, these results suggest that s.c. naratriptan doses similar to and above the oral therapeutic dose equivalent (single oral dose 2.5 mg) have no significant effect on peripheral blood flow as measured by FBF. S.c. naratriptan doses 1 mg, 5 mg, and 10 mg were well tolerated.
Yogendran
L
L
Glaxo Wellcome Clinical Pharmacology Unit, Northwick Park Hospital, Harrow, Middlesex, UK.
Boswell
D
D
Nacci
P
P
Winter
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012039:Regional Blood Flow; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D014363:Tryptamines
D007211:Indoles; D010880:Piperidines; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C106783:naratriptan