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 (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 blood 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 responders (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) were also significantly higher than the C(max) 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.