Desloratadine: A preclinical and clinical overview

A new competitive histamine H-1-receptor antagonist with superior binding a ffinity at this receptor as compared with other common antihistamines, desl oratadine is the active metabolite of loratadine, the most extensively used agent of this class. Under development for the treatment of allergic rhini tis and urticaria and currently awaiting regulatory approval in the United States, desloratadine was recently approved and became commercially availab le in Europe for the treatment of allergic disease. Desloratadine is at lea st 50-fold more potent in vitro and appears to be 10-fold more potent in vi vo than loratadine. The new antihistamine is metabolized to 3-hydroxydeslor atadine, which retains biological activity. Absorption of orally administer ed desloratadine is dose proportional, and desloratadine achieves steady-st ate concentrations after approximately 5 doses with once-daily administrati on. This is consistent with mean half-life values of 24-27 h and a 24-h dos ing interval. The absorption of desloratadine is not affected by food and t here are no clinically relevant drug-drug interactions. In randomized, doub le-blind, placebo-controlled clinical trials, a single 5 mg dose of deslora tadine conferred significant relief of seasonal allergic rhinitis (SAR) sym ptoms - including the complaint of nasal congestion within hours of the fir st dose, and these effects were sustained both for the entire 24-h dosing i nterval and up to 2-4 weeks with once-daily treatment (5 mg/day). In additi on, patients with seasonal exacerbations of mild to moderate asthma derived similar clinical benefits from desloratadine, with significant, first-dose relief of both SAR-related complaints such as nasal congestion as well as asthma symptoms. In addition, P, agonist requirements for symptom managemen t were significantly reduced from baseline in these asthma patients when tr eated with the 5 mg/day desloratadine regimen as compared with placebo. Als o experiencing marked relief of symptoms upon treatment with desloratadine were patients with chronic idiopathic urticaria, who exhibited significant first-dose relief of pruritus and sustained reductions in this symptom, num bers of lesions (and size of largest hive) and sleep disturbances, with a m arked improvement in their ability to carry out activities of daily living. The clinical benefits of desloratadine in the above clinical settings were accompanied by general improvements in quality of life. Desloratadine does not cross the blood-brain barrier, as demonstrated by both human studies u sing cognitive indices as well as work in animal models. Desloratadine is w ell tolerated, and no significant drug-related (or food-related) adverse ef fects were noted when the agent was administered together with cytochrome P 450 inhibitors (e.g., ketoconazole, erythromycin). Administration of deslor atadine has not been shown to cause any significant changes in cardiac acti vity at therapeutic doses, even at 9-fold higher doses, or in the presence of P450 inhibitors. Nor does administration of desloratadine lead to sedati on, even in the presence of alcohol. (C) 2001 Prous Science. All rights res erved.