Pharmacokinetic profile of alniditan nasal spray during and outside migraine attacks.

Abstract

AIMS:

To compare the pharmacokinetic profile of intranasal alniditan during and outside migraine attacks, and to investigate the relationship between initial rise of alniditan plasma concentration, and headache improvement.

METHODS:

Twenty-seven migraine patients (age: 18-65 years) were randomized to receive alniditan 2 mg or 4 mg, and investigated both during and outside a migraine attack. Maximal plasma concentrations (Cmax), time to Cmax (tmax), and the area under the curve over 2 h (AUC(0,2 h)), were calculated from the individual plasma concentration-time profile, obtained from 10 blood samples in each patient, during each of the two administrations.

RESULTS:

Alniditan was rapidly absorbed into the systemic circulation (tmax=11 min). All investigated pharmacokinetic parameters (Cmax, tmax, AUC(0,2 h)) were similar during and outside migraine attacks, both in the 2 mg (n = 13) and the 4 mg group (n = 14). In the 4 mg group, during attacks, mean plasma alniditan concentration at 5 min after administration (Ct=5) in responders (21+/-16 ng ml(-1); n=10) was significantly higher than the Ct=5 in nonresponders (3+/-3 ng ml(-1); P=0.01; n=4). However, the Cmax and AUC(0,2 h) in responders (33+/-18 ng ml(-1) and 12+/-6 ng ml(-1) h) were also significantly higher than the Cmax and AUC(0,2 h) in nonresponders (13+/-9 ng ml(-1); P=0.048 and 5+/-3 ng ml(-1) h; P=0.03).

CONCLUSIONS:

Absorption of alniditan nasal spray was not affected by migraine attacks, although 95% confidence intervals were wide. Early rise of plasma concentrations and the amount of drug in the circulation were related to headache improvement in the higher dose group.

• Authors: K I Roon, P A Soons, M P Uitendaal, F de Beukelaar, M D Ferrari
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 47 Issue 3 Pg. 285-90 (Mar 1999) ISSN: 0306-5251 [Print] England
• PMID: 10215753 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzopyrans
• Propylamines
• Pyrimidines
• Vasoconstrictor Agents
• alniditan

Topics

• Administration, Intranasal
• Adolescent
• Adult
• Aged
• Area Under Curve
• Benzopyrans (adverse effects, pharmacokinetics, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Migraine Disorders (drug therapy)
• Nasal Mucosa (drug effects)
• Propylamines (adverse effects, pharmacokinetics, therapeutic use)
• Pyrimidines (adverse effects, pharmacokinetics, therapeutic use)
• Taste Disorders (chemically induced)
• Vasoconstrictor Agents (adverse effects, pharmacokinetics, therapeutic use)