Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.     

Advances in allergy management

Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease-impaired quality of life. In vitro studies show that desloratadine, a new, once-daily, nonsedating, selective histamine H₁-receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and β₂-agonist medication use is decreased by desloratadine. Unlike many other second-generation histamine H₁-receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.     

The ARIA/EAACI criteria for antihistamines: an assessment of the efficacy, safety and pharmacology of desloratadine

Background:  The definition of allergic rhinitis and the classification of its severity and treatment have advanced in recent years following the publication of the Allergic Rhinitis and its Impact of Asthma (ARIA) document. The ARIA and the European Academy of Allergology and Clinical Immunology (ARIA/EAACI) have published a set of recommendations that outline the pharmacological and clinical criteria to be met by medications commonly used in the treatment of allergic rhinitis.
Methods:  An international group of experts met to assess the profile of the antihistamine, desloratadine, under the ARIA/EAACI criteria. Data on desloratadine were collected from peer-reviewed clinical studies and review articles, which were corroborated and augmented by comprehensive public access documents from the European Medicines Evaluation Agency (EMEA).
Results and conclusion:  Based on this systematic review, it was concluded that the efficacy, safety and pharmacology of desloratadine broadly meet the ARIA/EAACI criteria for antihistamines.     

药品行政保护品种介绍:抗组胺药(一)(待续)

地氯雷他定片剂通用名:地氯雷他定(desloratadine).商品名:Aerius片剂.化学名:8-氯-6,11-二氢-11-(4-哌啶亚基)-5H-苯[5,6]-环庚[1,2-b]吡啶.结构式见图1.     

去羧氯雷他定中有机溶剂残留量检查的研究

目的：测定去羧氯雷他定原料药中残留有机溶剂乙醇和乙酸乙酯的含量.方法：采用气相色谱法,顶空进样,FID检测器,以1,4-二氧六环为溶剂,异丙醇为内标,采用石英毛细管柱,以6%苯基-94%氰基丙基苯基二甲基聚硅氧烷为固定相,气化室150o C,检测器240o C,柱温65o C.结果：乙醇在10～220 μg/ml浓度范围内呈良好的线性关系（r＝0.999 9）,回收率为99.03%（RSD=2.5%）,最低检出限为1 μg/ml. 乙酸乙酯在10～200 μg/ml浓度范围内呈良好的线性关系（r＝0.999 9）,回收率为101.5%（RSD=1.2%）,最低检出限为3 μg/ml.三批去羧氯雷他定原料药中乙醇的残留量均为0.02%,乙酸乙酯的残留量均为0.03%.结论：本方法简单、快捷且灵敏度高,可用于去羧氯雷他定中乙醇和乙酸乙酯残留量的控制.     

地洛他定胶囊人体药动学和生物等效性评价

OBJECTIVETo study the pharmacokinetics and bioequivalence of desloratadine capsules and reference tablets in healthy volunteers. METHODSA single oral dose of 20mg desloratadine capsules and reference tablets were given to 20 healthy male volunteers in an     

地洛他定胶囊人体药动学和生物等效性评价

目的:研究地洛他定胶囊和地洛他定片在人体的药动学和生物等效性.方法:20名健康受试者随机交叉单剂量口服地洛他定胶囊或地洛他定片20 mg后,采用高效液相色谱-质谱联用(HPLC-MS)测定血浆中地洛他定的经时血药浓度,计算其药动学参数和相对生物利用度,评价两种制剂的生物等效性.结果:经3P97拟合,两者的体内过程皆符合血管外口服给药一室模型,采用梯形法计算的两者AUC0-72分别为(238.2±57.2)μg·h·L-1和(247.7±73.3)v·h·L-1,Cmax均值分别为(13.7±4.3)μg·L-1和(14.3±4.5)μg·L-1,tmax均值分别为(2.2±0.7)h和(2.3±0.9)h,地洛他定胶囊对地洛他定参比片的相对生物利用度为(96.4±6.3)%.结论:统计学分析结果显示,两种制剂具有生物等效性.     

H1‐antihistamines and urticaria: how can we predict the best drug for our patient?

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H₁‐antihistamines currently available and the pharmaceutical industries need to keep developing H₁‐antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head‐to‐head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H₁‐antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H₁‐antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine‐induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.     

Combining desloratadine and pseudoephedrine in the treatment of seasonal allergic rhinitis

Nonsedating antihistamines are a first-line therapy in the management of allergic rhinitis. They relieve the majority of the histamine-mediated symptoms of the condition, including rhinorrhea, sneezing, and pruritus. The nonsedating antihistamine desloratadine is effective in alleviating the symptoms of both seasonal and perennial allergic rhinitis. It may also have some decongestant properties, and thus help to alleviate nasal congestion. Administering desloratadine in combination with the decongestant pseudoephedrine may offer allergic rhinitis patients with moderate-to-severe nasal congestion the benefits of desloratadine’s effectiveness for alleviating histamine-mediated symptoms plus pseudoephedrine’s relief from nasal congestion. This drug profile reviews a combination therapy containing desloratadine and pseudoephedrine, approved in the USA for the relief of the symptoms of seasonal allergic rhinitis, including nasal congestion.