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Preliminary Studies of the Pharmacokinetics and Tolerability of Zolmitriptan Nasal Spray in Healthy Volunteers
Author(s) -
Yates Roger,
Nairn Kevin,
Dixon Ruth,
Seaber Emma
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127002762491325
Subject(s) - zolmitriptan , nasal spray , pharmacokinetics , medicine , nasal administration , tolerability , pharmacology , oral administration , crossover study , bioequivalence , anesthesia , sumatriptan , placebo , adverse effect , receptor , alternative medicine , pathology , agonist
Two preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray were conducted, each involving 12 healthy volunteers. In study 1, an initial double‐blind, dose escalation phase (placebo or 2.5, 5.0, or 10 mg zolmitriptan intranasally) was followed by an open crossover phase in which all subjects received 10 mg zolmitriptan as a nasal spray, tablet, and oral solution. In study 2, subjects received, on three separate occasions, zolmitriptan 2.5 mg as an intranasal solution at pH7.4, at pH 5.0, and as an oral tablet. In study 1, plasma concentrations of zolmitriptan and its active metabolite, 183C91, were broadly dose proportional. Plasma concentrations of zolmitriptan were detected earlier following nasal spray administration than after either tablet or oral solution. Similarly, in study 2, zolmitriptan was absorbed more rapidly following nasal spray administration with detectable plasma concentrations 5 minutes after dosing. Plasma levels were maintained at a plateau between 1 and 6 hours postdose, then decreased with a half‐life of approximately 3 hours. There was no statistically significant difference for AUC or C max values between the two nasal spray solutions or between nasal spray and oral formulations. Other pharmacokinetic parameters for zolmitriptan were similar between the formulations. Plasma concentrations of 183C91 were higher for the first 2 hours after oral than after nasal spray administration. All formulations of zolmitriptan were well tolerated.