Evaluation of the Effect of Xylometazoline on the Absorption of Zolmitriptan Nasal Spray

Abstract

Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is highly effective for the acute treatment ofmigraine.[1] Following oral administration, zolmitriptan is metabolised to three major metabolites, two of which are inactive. The active Ndesmethyl metabolite (183C91) is also a 5-HT1B/1D receptor agonist that is two to six timesmore potent in animal models than zolmitriptan.[2] A nasal spray formulation of zolmitriptan has been developed that may have several advantages over conventional oral preparations. Nasal administration gives rise to a more rapid absorption of zolmitriptan than the tablet formulation.[3,4] Furthermore, nasal administration may be preferable for those who experience nausea or vomiting during migraine attacks, or those who have difficulty swallowing a tablet. Sympathomimetic nasal decongestants such as xylometazoline are commonly used to relieve the symptoms of nasal congestion, hayfever or rhinitis. Vasoconstriction induced by these agents may reduce nasal blood flow for up to 12 hours and therefore may affect the absorption of other intranasal medications. The purpose of this study was to investigate the effects of xylometazoline on the absorption of zolmitriptan nasal spray. Methods