Pharmacokinetic profile of alniditan nasal spray during and outside migraine attacks

Aims To compare the pharmacokinetic profile of intranasal alniditan during and outside migraine attacks, and to investigate the relationship between i nitial rise of alniditan plasma concentration, and headache improvement. Methods Twenty-seven migraine patients (age: 18-65 years) were randomized t o receive alniditan 2 mg or 4 mg, and investigated both during and outside a migraine attack. Maximal plasma concentrations (C-max), time to C-max (t( max)), 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 blo od samples in each patient, during each of the two administrations. Results Alniditan was rapidly absorbed into the systemic circulation (t(max )=11 min). All investigated pharmacokinetic parameters (C-max, t(max), 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 (C-t=5) in re sponders (21 +/- 16 ng ml(-1); n=10) was significantly higher than the C-t= 5 in nonresponders (3 +/- 3 ng ml(-1); P=0.01; n=4). However, the C-max and AUC(0,2 h) in responders (33 +/- 18 ng ml(-1) and 12 +/- 6 ng ml(-1) h) we re also significantly higher than the C-max, and AUC(0,2 h) in nonresponder s (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 migrain e attacks, although 95% confidence intervals were wide. Early rise of plasm a concentrations and the amount of drug in the circulation were related to headache improvement in the higher dose group.