Fexofenadine: a review of its use in the management of seasonal allergic rhinitis and chronic idiopathic urticaria

Fexofenadine, the active metabolite of terfenadine, is a selective histamine H1 receptor antagonist that does not cross the blood brain barrier and appears to display some anti-inflammatory properties. Fexofenadine is rapidly absorbed (onset of relief < or = 2 hours) and has a long duration of action, making it suitable for once daily administration. Clinical trials (< or = 2 weeks' duration) have shown fexofenadine 60 mg twice daily and 120 mg once daily to be as effective as loratadine 10 mg once daily, and fexofenadine 120 mg once daily to be as effective as cetirizine 10 mg once daily in the overall reduction of symptoms of seasonal allergic rhinitis. When given in combination, fexofenadine and extended release pseudoephedrine had complementary activity. Fexofenadine was effective in relieving the symptoms of sneezing, rhinorrhoea, itchy nose palate or throat, and itchy, watery, red eyes in patients with seasonal allergic rhinitis. There were often small improvements in nasal congestion that were further improved by pseudoephedrine. Fexofenadine produced greater improvements in quality of life than loratadine to an extent considered to be clinically meaningful, and enhanced patients' quality of life when added to pseudoephedrine treatment. Although no comparative data with other H1 antagonists exist, fexofenadine 180 mg once daily was effective in reducing the symptoms of chronic idiopathic urticaria for up to 6 weeks. Fexofenadine was well tolerated in clinical trials in adults and adolescents and the adverse event profile was similar to placebo in all studies. The most frequently reported adverse event during fexofenadine treatment was headache, which occurred with a similar incidence to that seen in placebo recipients. Fexofenadine does not inhibit cardiac K+ channels and is not associated with prolongation of the corrected QT interval. When given alone or in combination with erythromycin or ketoconazole, it was not associated with any adverse cardiac events in clinical trials. As it does not cross the blood brain barrier, fexofenadine is free of the sedative effects associated with first generation antihistamines, even at dosages of up to 240 mg/day. CONCLUSIONS: fexofenadine is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria for which it is a suitable option for first-line therapy. Comparative data suggest that fexofenadine is as effective as loratadine or cetirizine in the treatment of seasonal allergic rhinitis. In those with excessive nasal congestion the combination of fexofenadine plus pseudoephedrine may be useful. In clinical trials fexofenadine is not associated with adverse cardiac or cognitive/psychomotor effects.     

The utility of mixed-effects covariate analysis in rapid selection of doses in pediatric subjects: a case study with fexofenadine hydrochloride

Fexofenadine hydrochloride is a non-sedating antihistamine that is used in the treatment of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. A pooled analysis of pharmacokinetic data from children 6 months to 12 years of age and adults was conducted to identify the dose(s) in children that produce exposures comparable to those in adults for the treatment of seasonal allergic rhinitis. The pharmacokinetic parameter database included peak and overall exposure data from 269 treatment exposures from 136 adult subjects, and 90 treatment exposures from 77 pediatric allergic rhinitis patients. The data were pooled and analysed using NONMEM software, version 5.0. A covariate model based on body weight and age and a power function model based on body weight were identified as appropriate models to describe the variability in fexofenadine oral clearance and peak concentration, respectively. Individual oral clearance estimates were on average 44%, 36% and 61% lower in children 6 to 12 years (n=14), 2 to 5 years (n=21), and 6 months to 2 years (n=42), respectively, compared with adults. Trial simulations (n=100) were carried out based on the final pharmacostatistical models and parameter estimates to identify the appropriate dose(s) in children relative to the marketed dose of 60 mg fexofenadine hydrochloride in adults. The trials were designed as crossover studies in 18 subjects comprising various potential dosing regimens with and without weight stratification. Pharmacokinetic parameter variability was assumed to have a log-normal distribution. Individual weights and ages were simulated using mean (SD) estimates derived from the studies used in this analysis and proportional measurement/model mis-specification errors derived from the analysis were incorporated into the simulation. The results indicated that a 30 mg dose of fexofenadine hydrochloride administered to children 1 to 12 years of age and weighing >10.5 kg and a 15 mg dose administered to children 6 months and older and weighing 相似文献   

Fexofenadine in pediatrics: oral tablet and suspension formulations

Allergic rhinitis is a common chronic condition in children. Oral antihistamines are a first-line treatment option in allergic rhinitis and different formulations are available to aid administration to children. The tablet formulation of the second-generation antihistamine fexofenadine has established efficacy and safety in both adults and children. To aid administration in young children, a new oral suspension formulation of fexofenadine has been developed, indicated for the relief of seasonal allergic rhinitis symptoms in children aged 2-11 years and for uncomplicated skin manifestations of chronic idiopathic urticaria in children aged 6 months-11 years. Clinical studies have shown the oral suspension to have both bioequivalence with the 30 mg tablet formulation and a favorable safety and tolerability profile.     

匹多莫德联合非索非那定治疗慢性特发性荨麻疹50例疗效观察

目的观察非索非那定联合匹多莫德治疗慢性特发性荨麻疹的疗效。方法 100例患者随机分成两组,治疗组50例采用口服盐酸非索非那定片60mg,2次/d,连续治疗4周,同时口服匹多莫德分散片0.8g,1次/d,连续治疗4周;对照组50例单独口服盐酸非索非那定片,方法疗程同治疗组。结果治疗组总有效率为92.00%,对照组为76.00%,两组比较有统计学意义(χ2=5.26,P<0.05)。结论盐酸非索非那定片联合匹多莫德分散片治疗慢性特发性荨麻疹疗效确切。     

Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid.

Fexofenadine, a nonsedating antihistamine drug, is effective for the treatment of seasonal allergic rhinitis and chronic urticaria. Simultaneous administration of probenecid increases the plasma concentration of fexofenadine due to an inhibition of its renal elimination in healthy volunteers (Clin Pharmacol Ther 77:17-23, 2005). The purpose of the present study is to investigate the possibility that the drug-drug interaction between fexofenadine and probenecid involves the renal basolateral uptake process. The uptake of fexofenadine was determined in HEK293 cells expressing human organic anion transporter 1 (OAT1/SLC22A6), OAT2 (SLC22A7), OAT3 (SLC22A8), and organic cation transporter 2 (OCT2/SLC22A2). Only hOAT3-HEK showed a significantly greater accumulation of fexofenadine than that in vector-HEK, which was saturable with K(m) and V(max) values of 70.2 microM and 120 pmol/min/mg protein, respectively. Inhibition potency of probenecid for the uptake of fexofenadine was compared between hOAT3 and organic anion-transporting peptide 1B3 (hOATP1B3), a transporter responsible for the hepatic uptake of fexofenadine (Drug Metab Dispos 33:1477-1481, 2005). The K(i) values were determined to be 1.30 and 130 microM for hOAT3 and hOATP1B3, respectively, with Hill coefficients of 0.76 and 0.64, respectively. The K(i) value of probenecid for hOAT3, but not for hOATP1B3, was significantly lower than the maximum unbound plasma concentration of probenecid at clinical dosages. These results suggest that the renal drug-drug interaction between fexofenadine and probenecid is probably explained by an inhibition of the renal uptake of fexofenadine via hOAT3, at least in part.     

Ebastine: an update of its use in allergic disorders

Ebastine is a second-generation antihistamine which undergoes transformation to its active metabolite, carebastine. Its antihistaminic and antiallergic effects have been demonstrated in in vitro and in vivo studies, in addition to data obtained from clinical trials. Patients with allergic rhinitis or chronic idiopathic urticaria experienced significant improvement in their symptoms with ebastine 10 or 20 mg once daily. Some studies in patients with seasonal allergic rhinitis (SAR) have indicated trends towards greater efficacy with the 20 mg than the 10 mg dose, although only 1 study has shown statistically significant benefits. In comparative trials in patients with SAR, ebastine 10 mg was as effective as most other second-generation antihistamines, including astemizole, azelastine, cetirizine, loratadine and terfenadine. Ebastine 20 mg/day was significantly superior to loratadine 10 mg/day in patients with SAR according to effects on secondary efficacy variables in comparative studies; 1 study found significantly greater changes from baseline in mean total symptom score with ebastine 20 mg (-43 vs -36% with loratadine, p = 0.045). In patients with perennial allergic rhinitis, ebastine 10 or 20 mg daily was significantly more effective than loratadine in reducing total symptom scores from baseline 1 comparative study. There have been no reports of serious adverse cardiac effects during ebastine therapy. Increases in corrected QT interval have been observed during clinical trials; however, these have not been considered clinically significant and were generally of similar magnitude to those seen with loratadine. The normal diurnal variation in QTc interval and the problems associated in correcting for changes in heart rate also complicate assessment of this issue. The incidence of adverse events during ebastine treatment is not significantly greater than that observed with placebo or other second-generation antihistamines. Conclusions: Ebastine 10 mg daily is a well tolerated and effective treatment for allergic rhinitis and chronic idiopathic urticaria. At this dosage, it is as effective as the other second-generation antihistamines against which it has been compared. Ebastine 20 mg has similar tolerability to the 10 mg dose, and trends towards greater efficacy with the higher dose have been shown in some studies. Ebastine does not appear to be associated with any significant cardiac adverse events. Ebastine is a useful treatment option for patients with allergic rhinitis or chronic idiopathic urticaria.     

抗组胺药非索非那定的研究进展

非索非那定是第二代H1抗组胺药,对H1受体有高度选择性,有直接的抗炎活性,起效快、作用维持时间长且长期使用不易出现耐药性.非索非那定的代谢动力学易受几种转运蛋白诱导剂或抑制剂的影响,但未见需调整剂量的报道,转运蛋白对非索非那定代谢的机理有待进一步的研究.临床用于治疗变态反应性疾病,如过敏性鼻炎、荨麻疹、过敏性哮喘、遗传性过敏性斑秃等,且联合其他药物疗效显著.目前,非索非那定微球的鼻内给药制剂正在研发中.非索非那定不良反应少见,无论是单独应用还是联合其他药物使用,都未见严重的心血管事件,不影响胆碱能活性.非索非那定不能透过血脑屏障、不进入中枢神经系统,被推荐于从事安全相关作业人员使用.     

依巴斯汀治疗慢性特发性荨麻疹及过敏性鼻炎

目的　评价国产依巴斯汀治疗慢性特发性荨麻疹和过敏性鼻炎的临床疗效和安全性。方法　采用随机、双盲、平行组对照的方法 ,对依巴斯汀进行Ⅱ期临床试验。依巴斯汀组 135例 ,其中慢性荨麻疹 6 9例 ,过敏性鼻炎 6 6例 ;西替利嗪 (对照 )组 132例 ,其中慢性荨麻疹 6 7例 ,过敏性鼻炎 6 5例 ;两组病人均每天 1次口服观察药 1片 (10mg) ,连续用药 14天。结果　依巴斯汀组的慢性荨麻疹、过敏性鼻炎的总有效率分别为 91 3%和 89 4 % ,而对照组分别为 87 9%和 84 6 % ,两组间均无显著差异 (P >0 0 5 )。两种药物的不良反应主要为轻、中度困倦和口干 ,两组间无显著差异 (P>0 0 5 )。结论　依巴斯汀治疗慢性特发性荨麻疹和过敏性鼻炎安全有效 ,其疗效及不良反应与西替利嗪相似。     

非索非那定与西替利嗪随机对照治疗变应性鼻炎的临床试验

目的:比较非索非那定与西替利嗪治疗变应性鼻炎的疗效及安全性。方法:采用多中心、随机、双盲双模拟、平行对照的临床试验。试验组变应性鼻炎病人68例,用非索非那定片,120mg,po,qd;对照组病人72例,用西替利嗪片,10mg,po,qd。2组均连续服药14d。对治疗前后病人的喷嚏、流涕、鼻塞、鼻痒及鼻腔情况进行评分。结果:试验组和对照组治疗变应性鼻炎的有效率分别为99%,93%;药物不良反应发生率分别为22%,25%。2组差异均无显著意义(P>0.05)。结论:非索非那定治疗变应性鼻炎安全有效,与西替利嗪相仿。     

The effects of fexofenadine on eosinophilia and systemic anaphylaxis in mice infected with Trichinella spiralis

BACKGROUND: The effects of the non-impairing, H(1)-receptor antagonist fexofenadine were investigated in in vivo mouse models of eosinophilia and systemic anaphylaxis. METHODS: Eosinophilia was investigated in C57BL/6 mice (n=5 per group) infected with Trichinella spiralis, with and without administration of fexofenadine HCl (5, 10 and 20 mg/kg/day). Eosinophilia was also studied, with and without fexofenadine administration, in mice with a congenital mast-cell deficiency (W/W(v)) and controls (+/+). The effect of fexofenadine HCl (20 mg/kg/day) on IL-5 and eotaxin blood levels was also investigated in C57BL/6 mice. In a separate model, systemic anaphylaxis was induced in C57BL/6 mice using T. spiralis antigen. Fexofenadine HCl (5, 10 and 20 mg/kg) or vehicle was administered 20 min before antigen challenge (n=5 per group). The effect of fexofenadine on systemic anaphylaxis caused by IgE and anti-IgE was also examined in CBF1 mice injected with serum from NC/Nga mice with high IgE levels. Rectal temperature was measured as an indicator of anaphylaxis. RESULTS: In C57BL/6 mice, repetitive oral administration of fexofenadine HCl (5, 10 and 20 mg/kg/day) resulted in dose-dependent suppression of eosinophilia (p<0.05-0.0001). No suppression was observed in mast-cell deficient W/W(v) mice. In addition, single oral administration of fexofenadine HCl (10 and 20 mg/kg) significantly suppressed the decrease in rectal temperature (p<0.01), a marker for systemic anaphylaxis, in C57BL/6 mice. In CBF1 mice injected with serum from NC/Nga mice with high IgE levels, the decrease in rectal temperature was suppressed by single administration of fexofenadine HCl (10 and 20 mg/kg; p<0.01 and p<0.001, respectively). Fexofenadine had no effect on peripheral IL-5 and eotaxin levels. CONCLUSION: These results indicate that fexofenadine suppresses both eosinophilia and systemic anaphylaxis, both of which are fundamental reactions in allergic diseases.     

Levocetirizine: a review of its use in the management of allergic rhinitis and skin allergies

Levocetirizine (Xyzal) is a selective, potent, oral histamine H(1) receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU). Large, well designed trials indicate that levocetirizine is effective and generally well tolerated in the treatment of allergic rhinitis and CIU. Its pharmacological profile offers many positive aspects: a rapid onset and long duration of antihistaminic effect; rapid absorption and high bioavailability; a low potential for drug interactions; a low volume of distribution; and a lack of effect on cognition, psychomotor function and the cardiovascular system. Allergen challenge chamber studies suggest that levocetirizine has better efficacy than desloratadine, loratadine or fexofenadine. Well controlled, long-term studies with other later-generation H(1) receptor antagonists are required to fully define its clinical profile relative to other agents in this class. Overall, levocetirizine is a valuable addition to the oral H(1) receptor antagonists available for the treatment of allergic rhinitis and as first-line therapy in patients with CIU.     

A review of the second-generation antihistamine ebastine for the treatment of allergic disorders

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.     

A review of the second-generation antihistamine ebastine for the treatment of allergic disorders

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5 – 10 and 2.5 mg, appears to be efficient and can be used safely in children 6 – 11 and 2 – 5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.     

The safety and efficacy of desloratadine for the management of allergic disease.

Allergic disease is an increasing problem worldwide. Allergic rhinitis, an inflammatory response to an allergen, affects an estimated 20-40 million people in the US, while chronic idiopathic urticaria is a dermatoallergic condition that affects 0.1-3% of people in the US and Europe. The primary goals of treatment for allergic rhinitis are to reduce symptoms, which include sneezing, rhinorrhoea and nasal congestion, improve quality of life and prevent the sequelae associated with this disease, while the goal for chronic idiopathic urticaria is the rapid and prolonged control of symptoms. Quantitatively, histamine is the most abundant mediator present during an allergic episode - thus, antihistamines (historically called histamine H(1) receptor antagonists, now called H(1) receptor inverse agonists) are a first-line defense against allergic rhinitis and chronic idiopathic urticaria. Although first-generation antihistamines can cause sedation and cognitive impairment, second-generation antihistamines are relatively non-sedating and free of such adverse events owing to their comparative inability to penetrate the blood-brain barrier. Desloratadine is one such second-generation antihistamine and is indicated for the treatment of allergic diseases, including allergic rhinitis and chronic idiopathic urticaria. It has proven efficacy against the symptoms associated with seasonal and perennial allergic rhinitis, including nasal congestion, and chronic idiopathic urticaria. As a result, it has been shown to improve patients' quality of life. The safety and efficacy profiles of desloratadine are well established, and published postmarketing analyses have assessed >54 000 patients. Although earlier second-generation antihistamines have been associated with cardiovascular adverse effects, desloratadine has been shown to be safe and well tolerated at nine times the recommended dose. In addition, it has been shown to not interact with concomitantly administered drugs and food. Overall, current data indicate that desloratadine is a safe and effective treatment for allergic diseases.     

Effects of fexofenadine hydrochloride in a guinea pig model of antigen-induced rhinitis

Allergic rhinitis is an inflammatory disease of the nasal mucosa, induced by histamine, leukotrienes, and other substances released from mast cells. Fexofenadine hydrochloride, the active metabolite of terfenadine, is a novel, nonsedating antiallergic drug having H1 receptor antagonistic activity. Fexofenadine is effective for the treatment of allergic rhinitis. However, its mechanism of action in attenuating nasal congestion has not yet been elucidated. Therefore, we first examined the effects of fexofenadine on a guinea pig model of antigen-induced rhinitis. We also evaluated the effects of mepyramine, zafirlukast and ramatroban in this model; these drugs are an H1 receptor antagonist, a selective leukotriene antagonist and a selective thromboxane antagonist, respectively. Rhinitis was induced by ovalbumin (OVA) instillation into the nasal cavity of animals that had been sensitized by two earlier OVA injections (s.c. and i.p.). The nasal airway resistance was measured for 45 min after the challenge. Fexofenadine hydrochloride (20 mg/kg) and terfenadine (20 mg/kg) administered orally 70 min prior to the challenge significantly inhibited (fexofenadine, p < 0.001, terfenadine, p < 0.05) the increase in nasal airway resistance. Ramatroban (30 mg/kg) administered orally 60 min prior to the challenge also significantly inhibited (p < 0.05) the increase in nasal airway resistance. In contrast, mepyramine (3 mg/kg i.v.) and zafirlukast (3 mg/kg p.o.) failed to reduce the increase in nasal airway resistance. These results suggest that thromboxane may be involved in the increase in the nasal airway resistance in this model. Accordingly, fexofenadine may reduce the increase in nasal airway resistance by inhibiting the release of chemical mediators, including thromboxane, that are involved in the increase in nasal airway resistance in this model.     

Dose proportionality and comparison of single and multiple dose pharmacokinetics of fexofenadine (MDL 16 455) and its enantiomers in healthy male volunteers

The pharmacokinetics and dose proportionality of fexofenadine, a new non-sedating antihistamine, and its enantiomers were characterized after single and multiple-dose administration of its hydrochloride salt. A total of 24 healthy male volunteers (31±8 years) received oral doses of 20, 60, 120 and 240 mg fexofenadine HCl in a randomized, complete four-period cross-over design. Subjects received a single oral dose on day 1, and multiple oral doses every 12 h on day 3 through the morning on day 7. Treatments were separated by a 14-day washout period. Serial blood and urine samples were collected for up to 48 h following the first and last doses of fexofenadine HCl. Fexofenadine and its R(+) and S(−) enantiomers were analysed in plasma and urine by validated HPLC methods. Fexofenadine pharmacokinetics were linear across the 20–120 mg dose range, but a small disproportionate increase in area under the plasma concentration–time curve (AUC) (<25%) was observed following the 240 mg dose. Single-dose pharmacokinetics of fexofenadine were predictive of steady-state pharmacokinetics. Urinary elimination of fexofenadine played a minor role (10%) in the disposition of this drug. A 63:37 steady-state ratio of R(+) and S(−) fexofenadine was observed in plasma. This ratio was essentially constant across time and dose. R(+) and S(−) fexofenadine were eliminated into urine in equal rates and quantities. All doses of fexofenadine HCl were well tolerated after single and multiple-dose administration. © 1998 John Wiley & Sons, Ltd.     

Some pharmacokinetic aspects of the lipophilic terfenadine and zwitterionic fexofenadine in humans

Fexofenadine, an active metabolite of the second-generation histamine H1 receptor antagonist (antihistamine) terfenadine, does not have the disadvantage of QT prolongation. In addition, unlike first-generation antihistamines, it is associated with few CNS adverse effects. Chemically, fexofenadine has a zwitterionic structure that makes it an interesting molecule for use as an oral drug. Fexo-fenadine has negligible hepatic metabolism in humans, and is recovered mainly in the faeces in an unchanged form after oral administration. The absolute oral bioavailability of fexofenadine in humans is not known because of a lack of studies of intravenous administration of this agent. Its apparent elimination half-life (t1/2) ranges from 3 to 17 hours and is highly dependent on study design, i.e. the length of blood sampling. This large discrepancy might be associated with a 'flip-flop' phenomenon caused by slow absorption of the zwitterionic molecule. This review summarises the available literature related to the absorption, elimination and excretion of fexofenadine and terfenadine. Based on these data, the volume of distribution, t1/2 and oral bioavailability of fexofenadine in humans are estimated. Understanding these pharmacokinetic aspects of this drug might be very useful for medicinal chemists utilising fexofenadine/terfenadine as an example for designing zwitterionic compounds to combat cardiotoxicity and other issues related to basic and lipophilic molecules.     

Pharmacokinetic evaluation of levocetirizine

INTRODUCTION: There have recently been guidelines developed for the diagnosis and treatment of rhinitis and urticaria. For both conditions, second-generation antihistamines remain as the first-line therapy. AREAS COVERED: The article presents the current pharmacology, chemical properties, pharmacokinetics and metabolism of levocetirizine. The article also reviews the clinical efficacy of levocetirizine for seasonal allergic and perennial rhinitis, as well as chronic urticaria. The article is formed through the review of all the published literature in English retrieved from the PubMed/MEDLINE database between 1966 and March 2011 using the search terms: levocetirizine, allergic rhinitis, chronic urticaria and antihistamine. Furthermore, the article also reviews data provided by the manufacturer in addition to reports from governmental agencies. EXPERT OPINION: Levocetirizine has several pharmacokinetic properties that are desirable for an antihistamine providing a combination of both potency and safety. Its clinical advantages are derived from its rapid and extensive absorption, limited distribution and its very low degree of metabolism. Furthermore, levocetirizine scores very highly in terms of clinical efficacy as well as in patient/physician satisfaction studies. Given the lack of large multi-center studies that compare the treatment options for urticaria, clinicians must rely on potency studies when choosing treatment and levocetirizine does score very highly. However, other potent skin antihistamines, such as desloratadine or fexofenadine, should be preferred for patients who have a strict contraindication to the sedative effects of the drug.     

Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Azelastine is an antiallergic agent which demonstrates histamine H1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Azelastine antagonises histamine- and leukotriene-induced bronchospasm in animal studies and reduces airway responsiveness to inhaled antigen or distilled water, and exercise challenge. In comparative studies, orally administered azelastine in doses up to 4 mg/day consistently relieved symptoms in patients with seasonal or perennial rhinitis - comparable to inhaled sodium cromoglycate (cromolyn sodium) 80 mg/day, oral chlorpheniramine (chlorphenamine) and oral terfenadine 120 mg/day. In addition, azelastine administered as an intranasal spray was as effective as oral terfenadine 120 mg/day and intranasal budesonide 0.4 mg/day in alleviating symptoms of rhinitis. Azelastine is also a potent antiasthmatic agent which produces significant and long lasting bronchodilation in patients with bronchial asthma. The drug is superior to placebo and comparable to oral ketotifen 2 mg/day and sustained release theophylline 700 mg/day when administered as a twice daily oral 4 mg dose. Azelastine is generally well tolerated: the most common adverse effects are altered taste perception and drowsiness. Adverse effects are mild and transient and result in withdrawal of treatment in less than 2% of patients. In a comparative study oral azelastine 2 or 4 mg/day produced no more sedation than terfenadine 120 mg/day. Thus, barring unexpected findings with wider clinical use, azelastine offers an effective and well tolerated choice of treatment for patients with allergic rhinitis and/or bronchial asthma, which may be particularly beneficial in patients in whom inhaled drug treatment is contraindicated.     

Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation

Fexofenadine is a non-sedating selective third-generation antihistamine, which also exerts an anti-inflammatory action. The aim of this study was to evaluate the influence on the expression of inflammatory skin mediators, together with the efficacy and tolerability, of fexofenadine in chronic idiopathic urticaria (CIU). Fexofenadine 180mg was administered once daily for 4 weeks after a placebo run-in phase of 3 to 7 days. Efficacy paramaters were obtained from patients' assessment of urticaria symptoms. Non-lesional skin of patients with active CIU was studied immunohistochemically before and after treatment. The expression of the following mediators was evaluated: adhesion molecules (ICAM-1, ELAM-1, VCAM-1); mast cell proteases (chymase and tryptase) and proinflammatory cytokines (IL-1beta, IL-3, IL-6 and TNF-alpha). Of the 20 subjects enrolled, 3 dropped out of the study. Treatment proved successful in most cases (88.2%) (p <0.01) and a significant improvement of all symptoms was registered. Treatment was well-tolerated by all patients; adverse events, neither serious nor drug-related, occurred in any case. Immunochemistry revealed at the baseline a significant expression of ELAM-1, VCAM-1, tryptase, chymase, and TNF-alpha (p= 0.05) in non-lesional skin of patients compared to normal controls. After treatment with fexofenadine, there was a significant decrease in the expression of ELAM-1 (p= 0.02), VCAM-1 (p= 0.04) and tryptase (p= 0.04), whereas no relevant change was observed for the other parameters examined. This work confirms the efficacy and tolerability of fexofenadine HCl 180mg in CIU. These preliminary data show a trend towards a decrease in the expression of tryptase and some adhesion molecules after treatment, suggesting an anti-inflammatory activity of fexofenadine.