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.

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.

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.

Following treatment with MK-0524, the PD₇₅ (mean±SD) was significantly shifted from 15.8 ± 18.3 μg/nostril during the placebo period to more than 512 μg/nostril both following the 25- and 100-mg (maximum challenge dose tested) dose regimen.

Whether this >45 fold increase in PD₇₅ will induce a clinically meaningful effect of MK-0524 will require clinical study in participants with SAR.