The effect of MK-0524, a prostaglandin D2 receptor antagonist, on prostaglandin D2-induced nasal airway obstruction in healthy volunteers

• Published in: European journal of clinical pharmacology 2007-02, Vol.63 (2), p.135-141
• Main Authors: VAN HECKEN, A, DEPRE, M, GOTTESDIENER, K. M, DEUTSCH, P, CLEMENT, P, LAI, E, DE HOON, J. N, DE LEPELEIRE, I, THACH, C, OEYEN, M, VAN EFFEN, J, LAETHEM, T, MAZINA, K, CRUMLEY, T, WENNING, L
• Format: Article
• Language: English
• Subjects: Allergies; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Clinical trials; Drug therapy; Medical sciences; Mucous membrane; Nose; Pharmacology. Drug treatments; Pneumology
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-006-0211-2

Introduction Nasal congestion in allergic rhinitis results from tissue edema and vasodilatation in the nasal mucosa. Of the mediators released by mast cells in response to allergens, prostaglandin (PG) D2 is regarded as the most potent inducer of nasal congestion. Intranasal administration of PGD2 reproduces the nasal blockade experienced by patients with seasonal allergic rhinitis (SAR) via its action on the PGD2 (DP) receptor to induce nasal vasodilatation. Intranasal challenge with PGD2 can be a useful tool for evaluating DP-receptor antagonists. Objective The main purpose of this study was to examine the ability of MK-0524, a DP receptor antagonist in development for the treatment of SAR, to block PGD2 induced nasal congestion in healthy volunteers. Methods To this end, a double-blind, placebo-controlled, randomized, 3-period study was performed in 15 healthy subjects. During each period, subjects received MK-0524 25 mg, MK-0524 100 mg or placebo qd for 3 days. Twenty-four hours following the last dose, nasal provocations with PGD2 were performed to determine the PD75, which is the intranasal dose of PGD2 that provokes a 75% increase in baseline total nasal airway resistance as performed by active anterior rhinomanometry. Results Following treatment with MK-0524, the PD75 (mean+/-SD) was significantly shifted from 15.8+/-18.3 [mu]g/nostril during the placebo period to more than 512 [mu]g/nostril both following the 25- and 100-mg (maximum challenge dose tested) dose regimen. Conclusion Whether this >45 fold increase in PD75 will induce a clinically meaningful effect of MK-0524 will require clinical study in participants with SAR. [PUBLICATION ABSTRACT]