Acute effects of sumatriptan on aortic blood pressure, stiffness, and pressure waveform

• Published in: Clinical pharmacology and therapeutics 2006-07, Vol.80 (1), p.85-94
• Main Authors: Vanmolkot, Floris H M, Hoon, Jan N J M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arteries - diagnostic imaging; Blood Pressure - drug effects; Contraindications; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Sumatriptan - pharmacology; Ultrasonography; Vasoconstrictor Agents - pharmacology
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/j.clpt.2006.03.011

Background and Objectives Sumatriptan, a 5‐hydroxytryptamine (HT)1B/1D receptor agonist, is an effective acute antimigraine drug. Because of its vasoconstrictor activity, it is contraindicated in patients at high risk for adverse cardiovascular events. Acute antimigraine drugs without vasoconstrictor effects are currently being developed, and sensitive, noninvasive techniques by which to detect drug‐induced vascular effects would facilitate their clinical development. The effects of sumatriptan on aortic blood pressure, stiffness, and pressure waveform have not been assessed previously in detail. Methods A randomized, placebo‐controlled, double‐blind, 4‐way crossover study was performed in 12 healthy subjects. Each subject received 25, 50, and 100 mg sumatriptan and placebo as single oral doses. Vascular measurements, including oscillometric blood pressure measurement, arterial ultrasound, systolic pulse contour analysis, and aortic pulse wave velocity measurement, were performed at baseline and 30, 90, and 150 minutes after drug administration. Results Compared with placebo and expressed as weighted mean ± SD, 100 mg sumatriptan increased aortic systolic blood pressure by 6 ± 5 mm Hg (P < .01), aortic pulse wave velocity by 0.5 ± 0.5 m/s (P < .01), and aortic augmentation index by 13% ± 6% (P < .0001). The increase in aortic systolic blood pressure was larger compared with the increase in brachial systolic blood pressure (P < .0001). Significant vascular effects were already detected after the lowest dose of sumatriptan by systolic pulse contour analysis and arterial ultrasound. Conclusion These findings show that therapeutic doses of sumatriptan acutely increase aortic blood pressure, stiffness, and augmentation index. Noninvasive systolic pulse contour analysis and arterial ultrasound may facilitate detection of drug‐induced vascular effects in early clinical trials. Clinical Pharmacology & Therapeutics (2006) 80, 85–94; doi:10.1016/j.clpt.2006.03.011