Pharmacokinetic profile of alniditan nasal spray during and outside migraine attacks.
OBJECTIVE
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.
Roon
K I
KI
Department of Neurology, Leiden University Medical Centre, The Netherlands.
Soons
P A
PA
Uitendaal
M P
MP
de Beukelaar
F
F
Ferrari
M D
MD
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001578:Benzopyrans / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009297:Nasal Mucosa / Q000187:drug effects; D011437:Propylamines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013651:Taste Disorders / Q000139:chemically induced; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001578:Benzopyrans; D011437:Propylamines; D011743:Pyrimidines; D014662:Vasoconstrictor Agents; C100822:alniditan