Headache
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Randomized Controlled Trial Comparative Study
A Randomized Trial Comparing the Pharmacokinetics, Safety, and Tolerability of DFN-02, an Intranasal Sumatriptan Spray Containing a Permeation Enhancer, With Intranasal and Subcutaneous Sumatriptan in Healthy Adults.
Intranasal sumatriptan (Imitrex® ) may be an alternative for patients who refuse injections and cannot tolerate oral agents, but due to low bioavailability and slow absorption, the clinical utility of the currently marketed formulation is limited, highlighting an unmet need for an effective non-oral migraine medication with a rapid onset of action. To overcome the slow absorption profile associated with intranasal administration, we evaluated the impact of 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM, Intravail A-3™), a permeation enhancer, on sumatriptan's pharmacokinetic profile by comparing the pharmacokinetic characteristics of two commercial sumatriptan products, 4 mg subcutaneous and 6 mg subcutaneous in healthy adults, with DFN-02 - a novel intranasal agent comprised of sumatriptan 10 mg plus 0.20% DDM. We also determined the pharmacokinetic characteristics of DDM and evaluated its safety and tolerability. ⋯ In healthy subjects, DFN-02, an intranasal spray containing 10 mg sumatriptan plus DDM, had a more rapid absorption profile than commercially available intranasal sumatriptan 20 mg, and systemic exposure from a single-dose administration of DFN-02 was similar to 4 mg SC sumatriptan and two-thirds that of 6 mg SC sumatriptan. With DFN-02, plasma sumatriptan peaked 5 minutes earlier than with both subcutaneous formulations. Systemic exposure to sumatriptan was similar with DFN-02 and 4 mg subcutaneous sumatriptan; both yielded lower systemic exposure than 6 mg subcutaneous sumatriptan. Systemic exposure to DFN-02's excipient DDM was short-lived. DFN-02's safety and tolerability appear to be comparable to subcutaneous sumatriptan. Addition of a permeation enhancer improved the absorption profile compared with commercially available intranasal sumatriptan 20 mg.
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Whereas considerable data have been generated about the pathophysiology of pain processing during migraine attacks, relatively little is known about the neural basis of sensory hypersensitivity. In migraine, the term "hypersensitivity" encompasses different and probably distinct pathophysiological aspects of sensory sensitivity. During attacks, many patients have enhanced sensitivity to visual, auditory and/or olfactory stimuli, which can enhance headache while interictally, migraineurs often report abnormal sensitivity to environmental stimuli that can cause nonpainful discomfort. ⋯ The pathophysiological mechanisms and the origin of such sensitivity (individual predisposition to develop migraine disease or consequence of repeated migraine attacks) are ill understood. Functional neuroimaging and electrophysiological studies allow for noninvasive measures of neuronal responses to external stimuli and have contributed to our understanding of mechanisms underlying sensory hypersensitivity in migraine. The purpose of this review is to present pivotal neuroimaging and neurophysiological studies that explored the basal state of brain responsiveness to sensory stimuli in migraineurs, the alterations in habituation and attention to sensory inputs, the fluctuations of responsiveness to sensory stimuli before and during migraine attacks, and the relations between sensory hypersensitivity and clinical sensory complaints.
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Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co-occurrence have been described so far. ⋯ The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism.