Title: Does the unfavorable pharmacokinetic and pharmacodynamic profile of the iNOS inhibitor GW273629 lead to inefficacy in acute migraine?
Authors: Van Der Schueren, Bart ×
Lunnon, M W
Laurijssens, B E
Guillard, F
Palmer, J
Van Hecken, Anne
Depré, Marleen
Vanmolkot, F H
de Hoon, Jan #
Issue Date: Mar-2009
Series Title: Journal of clinical pharmacology vol:49 issue:3 pages:281-90
Abstract: The objective of this study was to investigate the pharmacodynamics and pharmacokinetics of a single dose of GW273629, a selective iNOS inhibitor, given during and outside a migraine attack. GW273629 1500 mg was administered to 15 migraine patients both ictally and interictally. Nasal and exhaled nitric oxide (NO), plasma 3-nitrotyrosine, and nitrates were measured to assess systemic NO production. In addition, pharmacokinetics and treatment response were assessed. Data are mean (95% confidence interval [CI]). Plasma 3-nitrotyrosine was higher ictally: 11.96 (8.22, 15.71) ictally versus 2.74 (2.24, 3.24) ng/10 mg interictally (P < .0001). Exhaled and nasal NO showed a similar trend: 12.5 (6.5, 18.6) and 62.2 (41.5, 82.8) ppb ictally versus 9.9 (6.3, 13.4) ppb and 52.5 (38.5, 66.0) ppb interictally, respectively. Early absorption of GW273629 (AUC(0-2) [90% CI]) was reduced by 41 (22, 55)% during an attack. There was no improvement of headache or associated symptoms. Migraine headache is associated with reduced early absorption of GW273629 and excess NO production. In this open-label study, GW273629 was ineffective in the treatment of acute migraine.
ISSN: 0091-2700
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Pharmacology Centre (-)
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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