Preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray in healthy volunteers.
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 pH 7.4, 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 AUG 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.
Yates
Roger
R
AstraZeneca, Macclesfield, Cheshire, United Kingdom.
Nairn
Kevin
K
Dixon
Ruth
R
Seaber
Emma
E
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010080:Oxazoles / Q000097:blood; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013607:Tablets; D013997:Time Factors; D014363:Tryptamines
D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D013607:Tablets; D014363:Tryptamines; C089750:zolmitriptan; C117402:183C91