Treatment Of Allergic Rhinoconjunctivitis Research Articles

Treatment with grass allergen peptides improves symptoms of grass pollen–induced allergic rhinoconjunctivitis

Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P=.0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P=.0403) in patients with more symptomatic ARC. No safety signals were detected. Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile.

ALLERGIC RHINOCONJUNCTIVITIS: CLINICAL FEATURES AND RATIONAL TREATMENT

One of the most common problems in basic treatment of allergic rhinoconjunctivitis (ARC) is concomitant viral infection. In these cases antiviral and immunomodulatory medications adding to the therapy could be useful. Recent data showed clinical efficacy of a new medication - allergoferon (recombinant human interferon α -2b + loratadine) in ARC treatment. The pharmacological action of allergoferon is achieved due to its antihistaminic, anti-itching, anti-exudative, anti-inflammatory, immunomodulatory, and antiviral properties. In this study clinical efficacy and safety of allergoferon in the treatment of allergic rhinoconjunctivitis has been shown.

Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study

BackgroundBilastine, a novel non-sedating second-generation H1-antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18–74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day −3 to 0) in total symptom score (TSS) at 2 weeks (Day 8–14), consisting of the itch and rash scores. ResultsA total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. ConclusionsTwo-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action.

Basic science for the clinician: Mechanisms of sublingual and subcutaneous immunotherapy

ObjectiveTo discuss the general immunologic changes that occur during immunotherapy, focusing on the differences between subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Data SourcesPubMed literature review. Study SelectionsArticles pertaining to SCIT and SLIT, with specific emphasis on those that included immune mechanistic studies. ResultsBoth SCIT and SLIT are characterized by the induction of regulatory B and T cells, decreased allergen-specific T-cell proliferation, a shift from a TH2 to TH1 cytokine milieu and from an IgE to an IgG4/IgA antibody response. These changes are accompanied by clinical improvement in symptoms. ConclusionImmunotherapy using allergen extracts administered via both subcutaneous and sublingual approaches have demonstrated efficacy in the treatment of allergic rhinoconjunctivitis and other allergic conditions. There are subtle differences between the approaches, and understanding these differences may help clinicians select a preferred route of therapy for particular patients or allergens, depending on the immune response that is being targeted.

Critical appraisal of the clinical utility of sublingual immunotherapy in allergy.

Since it was introduced by Noon in 1911, allergen-specific immunotherapy or desensitization has been widely prescribed in the management of allergic diseases. Aimed at the etiology, it represents the only effective treatment for allergy.The basic mechanisms of immunotherapy are becoming better understood and allow us to improve this technique in the future. The sublingual immunotherapy as an alternative to subcutaneous route has been widely studied. Several clinical trials confirmed that sublingual immunotherapy is efficient in reducing allergic respiratory symptoms. The sublingual immunotherapy reduces the risk of developing serious side effects due to desensitization.We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

Antihistamines for the Treatment of Allergic Rhino-conjunctivitis

Histamine plays an important role in the pathogenesis of allergic rhino-conjunctivitis (ARC). First generation antihistamines are sedative, they cause cognitive and psychomotor impairment, and they are not indicated for the treatment of ARC. Second generation H1-antihistamines, with their improved safety profile and faster and longer duration of action, meet many of the ARIA (Allergic Rhinitis and its Impact on Asthma) optimal antihistamine prerequisites for the treatment of ARC. They are recommended as first line therapy for the treatment of children and adults with ARC and are efficacious in rapidly reducing itching, sneezing and rhinorrhoea. However, they offer suboptimal relief to patients with significant nasal congestion. They are available as oral, intranasal and ocular preparations. Oral preparations are more effective when used continuously and have demonstrated a greater or similar efficacy to leukotriene receptor antagonists (LTRA), with a potentiated effect when used simultaneously. Second generation H1-antihistamines are recommended for both intermittent and persistent ARC and in combination with intranasal steroids (INS) for severe disease. Intranasal H1-antihistamine preparations have the advantage of being delivered directly to the nasal mucosa with faster onset of action (15 vs 60 min) and may be preferable when rapid symptom relief is desirable or for on-demand therapy. They are recommended for mild/intermittent disease. A better outcome is achieved when used in combination with INS. In particular, a single formulation of fluticasone with azelastine nasal spray has demonstrated superiority to monotherapy with either compound in patients with moderate/severe disease. Its use is recommended when monotherapy has proven insufficient and for the treatment of moderate/persistent disease. Ophthalmic preparations are efficacious in ameliorating ocular symptoms and can be used when oral antihistamines fail. In the management of ARC, second generation H1-antihistamine treatment reduces symptoms, improves quality of life, lessens the overall burden of disease and reduces disease-associated costs.

Allergy--current insights into prevention and diagnostic workup of immediate-type allergy and treatment of allergic rhinoconjunctivitis.

In recent decades, the incidence of allergic diseases has dramatically increased, by now affecting a large percentage of the population. For a long time, allergen avoidance was considered the most crucial measure in primary allergy prevention. However, studies have increasingly shown that exposure to allergens is an essential prerequisite for the development of immunological tolerance. Diagnostic workup is based on patient history, skin tests, and measurement of specific IgE antibodies. The introduction of component-based diagnostic workup offer an option to differentiate between primary sensitization and cross-reactivity caused by sensitization to panallergens or sensitization to cross-reactive carbohydrate epitopes. Symptomatic treatment only leads to temporary relief of allergic symptoms. By contrast, specific immunotherapy (SIT) may have long-lasting therapeutic effects and potentially even result in a complete cure. The selection of allergens for SIT is guided by the principle of major allergens. It is recommended to use those preparations that have been proven safe and effective in controlled clinical studies. With respect to subcutaneous immunotherapy, a host of tested and approved extracts are available for a wide range of different allergens. Large clinical trials have also confirmed the efficacy of sublingual immunotherapy with grass and also birch pollen extracts, which has led to the official approval of some preparations containing these allergens.

The Future of Sublingual Immunotherapy in the United States.

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

Bilastine: an environmental risk assessment

Context: Bilastine is a new oral selective, non-sedating histamine H1 antagonist for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. The European Medicines Agency requires an Environmental Risk Assessment (ERA) for all novel medicines for human use. Objective: To calculate the bilastine predicted environmental concentration in surface water (PECsw; phase I ERA), and to determine the effects of bilastine on aquatic systems (phase II [tier A]). Materials and methods: Bilastine PECsw was calculated using the maximum daily dosage (20 mg), assuming that all administered bilastine was released into the aquatic environment. A persistence, bioaccumulation and toxicity assessment was conducted using the log Kow from the molecular structure. In phase II (tier A), a ready biodegradability test was performed, and bilastine’s potential toxicity to various aquatic and sediment-dwelling micro-organisms was evaluated. Results: Bilastine PECSW was calculated as 0.1 μg L−1, and the compound was not readily biodegradable. Bilastine had no significant effects on Chironomus riparius midges, or on the respiration rate of activated sludge. For green algae, the bilastine no observed effect concentration (NOEC) was 22 mg L−1; bilastine had no effect on zebra fish development, or on the reproduction rate of daphnids. Discussion: Bilastine NOEC values against zebra fish, algae, daphnids, and aerobic organisms in activated sludge were at least 130 000-fold greater than the calculated PECSW value. Conclusion: No environmental concerns exist from bilastine use in patients with allergic rhinoconjunctivitis or urticaria.

PRS52 - Impact of Allergen Immunotherapy on Symptom-Free Days and Health Care Costs in Patients With Grass Pollen-Induced Allergic Rhinitis in Germany

• According to the World Health Organization (WHO), allergic respiratory diseases respiratory diseases have been recognized as the fourth most important chronic disease in the world and represent a major public health problem with significant quality of life (QoL) impairment. Approximately 90 million Europeans are affected by allergic respiratory diseases. • In Germany, 25% of the adult population and 21% of children suffer from allergic rhinoconjunctivitis (AR). • According to the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines, 10–40% of patients suffer from co-existing allergic asthma. • Treatment of AR mainly consists of symptom control achieved by allergen avoidance or use of symptomatic drug treatment (SDT). In poorly controlled AR patients in Germany, causal treatments such as allergen immunotherapy (AIT) may be required. A health economic assessment, reflective of German clinical practice, was conducted to determine the relative impact on clinical effects, expressed as SFD, and healthcare costs when treating patients with moderate-to-severe grass polleninduced allergic rhinoconjunctivitis with Oralair® or Grazax®.

Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis

Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in North America. To determine the efficacy and tolerability of standardized glycerinated short ragweed sublingual allergen immunotherapy liquid (RW-SAIL) extract in subjects with ragweed-related ARC. This phase 3, randomized, placebo-controlled trial was conducted in North America. Subjects (age range, 18-55 years) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed. Subjects self-administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season. The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores (TCS). During the entire season, there was a 43% decrease in TCS in subjects treated with RW-SAIL compared with placebo. Similar decreases were observed in TCS between the 2 groups during peak season (42%) and in daily symptom scores during the entire (42%) and peak (41%) seasons. The occurrence of adverse events was similar between the treatment groups; most were mild in severity. Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited. No anaphylaxis occurred. This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual standardized ragweed allergen immunotherapy liquid extract for the treatment of ARC.

Validation of Peptide Immunotherapy as a New Approach in the Treatment of Allergic Rhinoconjunctivitis: The Clinical Benefits of Treatment with Amb a 1 Derived T cell Epitopes

Validation of Peptide Immunotherapy as a New Approach in the Treatment of Allergic Rhinoconjunctivitis: The Clinical Benefits of Treatment with Amb a 1 Derived T cell Epitopes

The Efficacy of Dual Allergen Sublingual Immunotherapy in Subjects with Dermatophagoides farinae and Timothy Grass Allergy as Assessed by the Rhinoconjunctivitis Quality of Life Score

RATIONALE: We sought to evaluate the efficacy of dual allergen sublingual immunotherapy (SLIT) in subjects with Dermatophagoides farinae (DF) and Timothy Grass (TG) allergy using the Rhinoconjunctivitis Quality of Life (QOL) questionnaire.METHODS: This is a double-blind, placebo-controlled study in subjects with DF and TG allergy. Subjects were block randomized 2:1 (active drug:placebo). At the preliminary dosing visit, subjects received escalating doses of SLIT to a maximum dose. This dose was self-administered daily for 12 months. Subjects returned for follow up every 3-6 months. QOL questionnaires were administered at the preliminary visit and each follow up visit.RESULTS: Thirty subjects, age 5-57 years, were enrolled. Our preliminary data evaluates 21 subjects who have had at least 2 follow up visits. 18/21 (86%) subjects demonstrated improvement in mean QOL scores from baseline. 7/21 (33%) subjects had 50% or greater improvement in QOL scores from baseline.CONCLUSIONS: Preliminary data on subjects who received SLIT or placebo reveals that the majority showed improvement in QOL scores from baseline to first follow up visit. Given our 2:1 block randomization, a large number are likely those who received SLIT. We will further stratify our results once subjects are divided into treatment and placebo groups. To date, our data demonstrates that dual allergen SLIT is efficacious in the treatment of allergic rhinoconjunctivitis. RATIONALE: We sought to evaluate the efficacy of dual allergen sublingual immunotherapy (SLIT) in subjects with Dermatophagoides farinae (DF) and Timothy Grass (TG) allergy using the Rhinoconjunctivitis Quality of Life (QOL) questionnaire. METHODS: This is a double-blind, placebo-controlled study in subjects with DF and TG allergy. Subjects were block randomized 2:1 (active drug:placebo). At the preliminary dosing visit, subjects received escalating doses of SLIT to a maximum dose. This dose was self-administered daily for 12 months. Subjects returned for follow up every 3-6 months. QOL questionnaires were administered at the preliminary visit and each follow up visit. RESULTS: Thirty subjects, age 5-57 years, were enrolled. Our preliminary data evaluates 21 subjects who have had at least 2 follow up visits. 18/21 (86%) subjects demonstrated improvement in mean QOL scores from baseline. 7/21 (33%) subjects had 50% or greater improvement in QOL scores from baseline. CONCLUSIONS: Preliminary data on subjects who received SLIT or placebo reveals that the majority showed improvement in QOL scores from baseline to first follow up visit. Given our 2:1 block randomization, a large number are likely those who received SLIT. We will further stratify our results once subjects are divided into treatment and placebo groups. To date, our data demonstrates that dual allergen SLIT is efficacious in the treatment of allergic rhinoconjunctivitis.

Bilastine for the relief of allergy symptoms

Bilastine is a potent inhibitor of the histamine H1 receptor. It was recently approved in 28 countries of the European Union for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. Data from preclinical studies confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic and antiallergic properties in vivo. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. Bilastine has demonstrated a good safety profile, without serious adverse effects or antimuscarinic effects in clinical trials. There were no significant changes in laboratory tests, electrocardiograms or vital signs. In clinical studies, oral treatment with bilastine 20 mg once daily improved allergic rhinitis with greater efficacy than placebo and comparable to cetirizine and desloratadine. Bilastine 20 mg was more effective than placebo and equivalent to levocetirizine in chronic urticaria, relieving symptoms, improving quality of life and controlling sleep disorders.

Grass Pollen Immunotherapy as an Effective Therapy for Childhood Seasonal Allergic Asthma

Roberts G, Hurley C, Turcanu V, Lack G. J Allergy Clin Immunol. 2006;117:263–268 PURPOSE OF THE STUDY. There is abundant evidence to support the use of specific immunotherapy (SIT) in the treatment of allergic rhinoconjunctivitis. Studies that have looked at the role of SIT for the treatment of seasonal allergic asthma are lacking. This study evaluated the safety and effectiveness of SIT for the treatment of seasonal allergic asthma in children. STUDY POPULATION. A total of 39 of 161 screened subjects 3 to 16 years old were enrolled onto the study from the allergy clinic at St Mary's Hospital (London, United Kingdom). All of them had history of grass-pollen–induced asthma that required 200 μg of inhaled beclomethasone (or equivalent) daily. All subjects had a positive skin-prick–test response: a positive specific immunoglobulin E level (Pharmacia CAP) to a relevant grass pollen (Phleum pratense). Subjects also had a positive conjunctival provocation test. Subjects were excluded if they previously had been treated with grass-pollen immunotherapy or had a history of perennial asthma requiring inhaled corticosteroids, significant perennial allergic rhinitis, or sensitization to a pet present in the household. METHODS. The study was a single-center, randomized, double-blind, placebo-controlled study over 2 successive pollen seasons. Subjects were randomly assigned to receive SIT or placebo. The primary outcome was the asthma-symptom–medication score during the second pollen season. Secondary outcome measures included lung function, cutaneous, conjunctival, and bronchial allergen reactivity, and both exhaled nitric oxide and sputum eosinophil levels. RESULTS. The use of SIT was associated with a substantial reduction in asthma-symptom–medication score as compared with placebo (P = .04). There was significant reduction in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P = .01) reactivity to allergen after SIT compared with placebo. Children in the 2 groups had similar levels of airway inflammation, although less inhaled steroids were required for those in the active group. No serious adverse events were reported, and no subjects withdrew because of adverse events. CONCLUSIONS. SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen. REVIEWER COMMENTS. There are limited studies that have demonstrated the efficacy of immunotherapy for treatment of asthma. On the basis of the complex nature of asthma and realizing that multiple phenotypes exist, it is understandable that there is difficulty in evaluating SIT for asthma. This study provided encouraging evidence for the role of SIT in the treatment of seasonal allergic asthma. Unfortunately, the majority of allergic patients are sensitized to multiple allergens, and symptoms are typically triggered by several different allergens.

Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity

Cetirizine is an antihistamine, largely used in the treatment of allergic rhinoconjunctivitis, which also exerts anti-allergic activity. To evaluate cetirizine as treatment for children with rhinitis due to pollen allergy, and to evaluate its anti-allergic activity in such a clinical condition. The study was designed as parallel groups, double-blind, placebo-controlled, randomized. Twenty allergic children were enroled and subdivided in two groups, receiving a 4 week treatment during the pollen season. The following parameters were monitored: clinical symptoms evaluated by the allergist before and after treatment and by the patients through a daily diary card, inflammatory cells count, expression of ICAM-1 on nasal epithelial cells, inflammatory mediator levels in nasal lavage and peripheral blood before and after treatment, and pollen counts. This study shows that cetirizine treatment is able to reduce: clinical symptoms (P < 0.01), inflammatory cell infiltrate (P < 0.03), ICAM-1 expression on epithelial cells (P < 0.05), and soluble ICAM-1 (P < 0.05) and ECP (P < 0.05) in nasal lavage. Cetirizine is able to clinically improve nasal symptoms due to pollen allergy and to reduce allergic inflammation, which is related to allergen exposure.

Treatment of allergic rhinoconjunctivitis: a review of the role of topical levocabastine

Lcocabastine is an extremely potent and highly selective H1-receptor antagonist which has been specifically developed as eye drops and nasal spray for the treatment of allergic rhinoconjunctivitis. Clinical experience to date suggests that this topical antihistamine is at least as effective as other current first-line therapeutic approaches for the treatment of this condition, including oral H1-receptor antagonists and sodium cromoglycate. Onset of action is rapid, with clinical effects apparent within minutes of instillation. Moreover, duration of action is sufficiently long to permit a convenient twice-daily dosing regimen. Topical levocabastine is well tolerated with an adverse-effect profile comparable with that of placebo and sodium cromoglycate. As might be expected from the route of drug administration, application site reactions are the most frequent adverse effect associated with levocabastine eye drops and nasal spray with an incidence comparable with that seen in placebotreated controls. The availability of effective and well-tolerated topical antihistamines, such as levocabastine, is an important advance which broadens the range of therapeutic approaches available for the clinical management of allergic rhinoconjunctivitis. Levocabastine appears to be an attractive alternative to oral antihistamines as a first-line therapeutic option for the treatment of this atopic condition.

The pharmacology and use of H1-receptor-antagonist drugs.

The second-generation H1-antagonist drugs are supplanting their predecessors in the treatment of allergic rhinoconjunctivitis and chronic urticaria. Their use can be justified mainly on the basis of a more favorable risk-benefit ratio, because they are less toxic to the central nervous system. Future research into H1 antagonists should include additional dose-response studies in patients with allergic disorders, especially children and the elderly; objective studies of adverse effects; studies of topical mucosal application of H1 antagonists; and studies of H1-antagonist enantiomers and active metabolites. With the cloning of the gene encoding the H1 receptor and increased understanding of the precise structural requirements for H1-receptor activity, H1 antagonists with an even more favorable therapeutic index may be developed.

Pharmacokinetic Optimisation of Histamine H1-Receptor Antagonist Therapy

Second-generation, relatively nonsedating histamine H1-receptor antagonists (H1-RA) are extensively used worldwide for the symptomatic treatment of allergic rhinoconjunctivitis and chronic urticaria. Information about the pharmacokinetics and pharmacodynamics of these medications, while still incomplete, is now sufficient to permit optimisation of therapy. Published pharmacokinetic and pharmacodynamic information on these H1-RA is summarised here, and areas where more data are required are delineated. Serum concentrations of most second-generation H1-RA are relatively low, and are usually measured by radioimmunoassay. After oral administration, peak concentrations are observed within 2 or 3 h. Bioavailability has not been well studied, due to the lack of intravenous formulations. Most H1-RA are metabolised in the hepatic cytochrome P450 system: terfenadine, astemizole, loratadine, azelastine, and ebastine have 1 or more active metabolites which are present in serum in higher concentrations than the respective parent compound, and therefore can be measured by high performance liquid chromatography. Cetirizine, an active metabolite of the first generation H1-receptor antagonist hydroxyzine, is not further metabolised to any great extent in vivo, and is eliminated via renal excretion. Levocabastine is also eliminated primarily by excretion. Serum elimination half-life values differ greatly from 1 H1-RA to another, and are 24 h or less for terfenadine, astemizole, loratadine, cetirizine, azelastine and ebastine, and the active metabolites of terfenadine, loratadine and ebastine. The active metabolite of azelastine (demethylazelastine) has a serum elimination half-life value of about 2 days, while that of astemizole (demethyl-astemizole) has a value of 9.5 days. From the few published studies in which the apparent volumes of distribution of the second-generation H1-RA have been calculated, it appears that tissue distribution is extensive. In children, the half-lives of H1-RA are generally shorter than are found in adults; there is no published information on the pharmacokinetics of astemizole, loratadine, azelastine, or ebastine in children. In some elderly adults, terfenadine, loratadine and cetirizine may have longer half-lives than in young healthy adults. There is little published data on the pharmacokinetics of the second-generation H1-RA in patients with impaired hepatic function. The half-life of cetirizine is prolonged in those with impaired renal function. There is a paucity of information on the pharmacokinetics of H1-RA in neonates, in pregnancy or during lactation.(ABSTRACT TRUNCATED AT 400 WORDS)

Topical levocabastine, a selective H1 antagonist, in seasonal allergic rhinoconjunctivitis

Sixty-six patients with seasonal allergic rhinitis due to birch pollens, participated in an efficacy evaluation of topically applied, nasal and ocular, levocabastine, a highly selective H1 antagonist. A single blind comparison was performed between nasal levocabastine and flunisolide, a topical glucocorticoid preparation. Ocular levocabastine was compared with topical naphazoline/antazoline eye drops. Nasal and ocular symptom scores were recorded during a 31-day period. Pollen counts of birch pollens were done simultaneously. A global assessment of treatment efficacy was also made. In the comparison between the ocular treatments a significantly higher number of patients cited levocabastine excellent--it also had the advantage of fewer daily administrations. For nasal symptom scores the topical glucocorticosteroid therapy was in favour by number of sneezes. As for side effects, 44% of the patients complained of local irritation from naphazoline/antazoline eye drops or flunisolide nasal spray, but none with the levocabastine preparations. Topical levocabastine may provide an interesting alternative in the treatment of allergic rhinoconjunctivitis.