Desloratadine

Abstract: H1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H1-receptors which are members of the G-protein family. The older first generation H1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H1-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.

Abstract: Treatment for allergic conjunctivitis has markedly expanded in recent years, providing opportunities for more focused therapy, but often leaving both physicians and patients confused over the variety of options. As monotherapy, oral antihistamines are an excellent choice when attempting to control multiple earlyphase, and some late-phase, allergic symptoms in the eyes, nose and pharynx. Unfortunately, despite their efficacy in relief of allergic symptoms, systemic antihistamines may result in unwanted adverse effects, such as drowsiness and dry mouth. Newer second-generation antihistamines (cetirizine, fexofenadine, loratadine and desloratadine) are preferred over older first-generation antihistamines in order to avoid the sedative and anticholinergic effects that are associated with first-generation agents. When the allergic symptom or complaint, such as ocular pruritus, is isolated, focused therapy with topical (ophthalmic) antihistamines is often efficacious and clearly superior to systemic antihistamines, either as monotherapy or in conjunction with an oral or intranasal agent.

Abstract: Absorption, distribution, metabolism and excretion of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans have been compared. The time required to reach peak plasma levels (tmax) is shortest for levocetirizine (0.9 h) and longest for desloratadine (> or =3 h). Steady-state plasma levels are attained after about 6 days for desloratadine, 3 days for fexofenadine, 2-3 days for mizolastine and by the second day for levocetirizine. The apparent volume of distribution is limited for levocetirizine (0.4 L/kg) and mizolastine (1-1.2 L/kg), larger for fexofenadine (5.4-5.8 L/kg) and particularly large for desloratadine (approximately 49 l/kg). Fexofenadine and levocetirizine appear to be very poorly metabolized (approximately 5 and 14% of the total oral dose, respectively). Desloratadine and mizolastine are extensively metabolized. After administration of 14C-levocetirizine to healthy volunteers, 85 and 13% of the radioactivity are recovered in urine and faeces, respectively. In contrast, faeces are the preferential route of excretion for 14C-fexofenadine (80% vs. 11% of the radioactive dose in urine). The corresponding values are 41% (urine) and 47% (faeces) for 14C-desloratadine, 84-95% (faeces) and 8-15% (urine) for 14C-mizolastine. The absolute bioavailability is 50-65% for mizolastine; it is high for levocetirizine as the percentage of the drug eliminated unchanged in the 48 h urine is 77% of the oral dose; the estimation for fexofenadine is at least 33%; no estimation was found for desloratadine. Fexofenadine is a P-glycoprotein (P-gp) substrate and P-gp is certainly involved both in the poor brain penetration by the compound and, at least partially, in a number of observed drug interactions. An interaction of desloratadine with P-gp has been suggested in mice, whereas the information on mizolastine is very poor. The fact that levocetirizine is a substrate of P-gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P-gp-mediated drug interactions.

Abstract: Background: The evidence base for the use of H1-antihistamines in the treatment of perennial allergic rhinitis is considerably smaller than it is in the treatment of seasonal allergic rhinitis. Objective: We hypothesized that desloratadine, a new, nonsedating selective H1-antihistamine, would be efficacious and safe in the treatment of perennial allergic rhinitis. Methods: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, 676 patients with symptomatic perennial allergic rhinitis were randomly assigned to 4 weeks of treatment with either 5 mg of desloratadine once daily or placebo. Efficacy was assessed by using a morning-evening instantaneous total symptom score (TSS), which was composed of scores for 4 individual nasal symptoms (rhinorrhea, itching, sneezing, and postnasal drip) and 3 individual nonnasal symptoms (itching eyes, watering eyes, and itching of the ears or palate). Secondary outcome measures included a morning-evening reflective TSS, total nasal and nonnasal symptoms scores, and individual symptom scores. Safety evaluations, including 12-lead electrocardiograms, were performed. Results: Six hundred thirty-four patients completed the study. Desloratadine consistently diminished perennial allergic rhinitis symptoms, reducing the morning-evening instantaneous TSS (P = .005), the morning-evening reflective TSS (P = .007), the morning-evening reflective total nonnasal score (P = .023), and the individual nasal symptom scores for rhinorrhea, nasal itching, sneezing, and postnasal drip/drainage (P = .05 to P = .013) during weeks 1 through 4. Improvement in symptoms was observed after the first dose. Dropouts, and the type and frequency of adverse events (headache, viral infection, pharyngitis, and upper respiratory tract infection), were similar in both treatment groups. No clinically significant changes in QTc intervals were observed. Conclusions: Desloratadine rapidly and safely reduced the symptoms of perennial allergic rhinitis, and its efficacy did not diminish during 4 weeks of treatment. (J Allergy Clin Immunol 2003;111:617-22.)