Study of Sedative Tea Phytocomplex within the Framework of Studies Aimed at Creation of a Rectal Dosage Form with Antihistaminic Effect.

We designed a new complex drug with antiallergic effect containing, in addition to the main component loratadine, a phytocomplex for an extra therapeutic effect. A collection of plants with sedative activity is chosen and the optimal agent for extraction of bioactive compounds (40% ethanol) and optimal degree of plant fragmentation are determined. Chemical composition of the sedative tea is evaluated by reverse phase HPLC. The marker components of the species are detected: xanthohumol and isoxanthohumol - Humulus lupulus cone components, Mentha piperita rosmarinic acid, and scutellareine, Menyanthes trifolia element - quercetin-3-rutinoside, and caffeic acid. Standardization of the species by the absolute graduation method in conversion to quercetin-3-rutinoside is suggested.

H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review.

BACKGROUND: Anaphylaxis is a serious allergic or hypersensitivity reaction, which is rapid in onset and sometimes can prove fatal. Although H2-antihistamines are often administered for emergency treatment in anaphylaxis, there is uncertainty about their effectiveness in this disease. OBJECTIVE: To assess the benefits and harms of H2-antihistamines in the treatment of anaphylaxis. METHODS: A systematic review was performed of randomized controlled trials and quasi-randomized controlled trials comparing H2-antihistamines with placebo or no intervention in patients with anaphylaxis. RESULTS: The authors failed to identify any eligible studies for inclusion in this systematic review. CONCLUSION: When H2-antihistamines are recommended for anaphylaxis treatment, the status of the evidence base supporting their use should be described. Well-designed randomized controlled trials investigating the role of H2-antihistamines in anaphylaxis treatment are urgently needed.

Stereospecific versus nonstereospecific assessments for the bioequivalence of two formulations of racemic chlorpheniramine.

Chlorpheniramine (chlorphenamine, CPAM) is a racemic antihistaminic H1 drug containing two enantiomers. The aim of this study was to assess the bioequivalence of two formulations (reference and Vietnamese-tested formulation) of racemic chlorpheniramine combined with phenylpropanolamine in an open-labeled, randomized, crossover two-period study, after administration of 8 mg of racemic chlorpheniramine in 12 healthy Vietnamese subjects. First, dissolution of both formulations was tested in vitro according to USP requirements. Then the 12 subjects received both formulations after an overnight fast and a 7-day wash-out period. Plasma samples were collected up to 168 h. Plasma concentrations of total chlorpheniramine and its individual enantiomers were determined with a validated chiral HPLC method and pharmacokinetic parameters were estimated using model-independent analysis. For the reference formulation, Cmax and AUC values were higher for (+)S-chlorpheniramine ((+)S-CPAM) compared to (-)R-chlorpheniramine ((-)R-CPAM) (13.3 vs. 6.8 ng/ml and 409 vs. 222 ng/ml/h, respectively) while Clt/F and Vd/F were lower (9.8 vs. 17.6 l/h and 321 vs. 627 l, respectively). No difference was observed for Tmax, t(1/2), and MRT. Pharmacokinetic parameters were similar for the reference and the Vietnamese-tested formulation. Bioequivalence was assessed by Schuirmann test, as recommended by the current FDA and European Community criteria. Dissolution tests showed that both formulations were equivalent. A nonstereospecific, but not a stereospecific, approach indicated bioequivalence between the formulations.

Additive benefits of EFAs in dogs with atopic dermatitis after partial response to antihistamine therapy.

It has been reported that 20 to 70 per cent of atopic cases in the dog can be controlled with antihistamines, though the effective antihistamine cannot be predetermined. Combination therapy with essential fatty acids (EFAs) and antihistamines has been shown to be useful in dogs. All of the work published to date has been performed in open studies, without the use of placebo, and in dogs where the aim has been to control pruritus as a symptom rather than that caused specifically by atopy. The aim of this study was to assess the combined effects of four antihistamines; hydroxyzine, chlorpheniramine, cyproheptadine and clemastine; with both an EFA supplement and a placebo of olive oil, in 25 dogs to control pruritus in clinically proven cses of atopy.

Therapy for feline dermatoses.

This article compiles information on various therapies used in feline dermatology. Information on the following therapeutic agents and devices is discussed: antibiotics, antifungals, antileprosy drugs, antiparasiticides, antivirals, antihistamines, behavior modification drugs, fatty acids, progestogens, steroids, immunomodulating drugs, chemotherapeutic/immunosuppressive agents, retinoids, mechanical devices, hyposensitization, immunotherapy, food elimination trials, hypoallergenic diets, and miscellaneous topical agents such as polyhydroxydine solution, tar, and benzocaine-containing creams.

Ebastine in perennial allergic rhinitis.

Oral ebastine, 10 mg once daily for seven days, and placebo were compared as treatment for active perennial allergic rhinitis in 151 patients in a multicenter, randomized, double-blind trial. Ebastine treatment produced a significant reduction in the incidence and severity of most symptoms associated with perennial rhinitis. Tolerability was similar in the two treatment groups. The incidences of drowsiness and dry mouth were not more frequent in the patients treated with the active drug.

Comparative safety of H1 antihistamines.

In the allergic reaction, mast cells degranulate, releasing inflammatory mediators including histamine. The H1 receptor antihistamines have been developed over the past 50 years to minimize the clinical symptoms caused by this reaction. Currently, H1 antihistamines are taken by approximately 30 million Americans per year. First-generation H1 antihistamines, some of which are available without prescription, can cross the blood-brain barrier and have been reported to produce sedation in 10% to 25% of users. When activities that require mental alertness and concentration are considered--school performance and driving, for example--this effect is troublesome and even potentially hazardous. The newer, second-generation H1 antihistamines (eg, astemizole, cetirizine, loratadine, terfenadine) have difficulty entering the brain because they are typically large, lipophobic molecules that have charged side chains and are extensively bound to protein. Consequently, they appear to induce sedation less commonly than classic antihistamines. Since a primary tenet of medical care has always been primum non nocere--first of all, in the management of clinical illness, do no harm--it is important in these "State-of-the-Art Perspectives" to address the comparative safety of the H1 antihistamines. A number of methodologies have been used to make this assessment, including the multiple sleep latency test, the P300 (P3) wave of the auditory-evoked potential, self-ratings, visual function tests, and tests that measure reaction times, visual-motor coordination, and driving skills. The effect of the interaction of H1 antihistamines with alcohol and tranquilizers also has been examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative efficacy of H1 antihistamines.

Second-generation H1 receptor antagonists (cetirizine, terfenadine, astemizole, loratadine, azelastine, and acrivastine) offer several important advantages over the older first-generation antihistamines. They are substantially less sedating and have little or no anticholinergic activity. Many of them are effective for 12 to 24 hours, thereby increasing compliance. In addition to acting as competitive inhibitors of histamine, several seem to have other antiallergic mechanisms as well. They are all absorbed well when taken orally. Many studies demonstrate their effectiveness compared with placebo in the treatment of seasonal and perennial rhinitis and chronic urticaria, and several studies suggest that they have a role in the treatment of bronchial asthma. A number of multicenter, double-blind, placebo-controlled studies comparing the effectiveness of terfenadine, 60 mg bid, with chlorpheniramine, 8 mg bid, in seasonal allergic rhinitis demonstrate that both drugs are approximately equally potent in reducing the symptoms of sneezing, rhinorrhea, and nasal itching and are statistically significantly better than placebo. Ocular symptoms were reduced somewhat less but still significantly. No differences from placebo were recorded in their effect on nasal congestion. The effectiveness of cetirizine, 10 mg once daily, compared with astemizole, 10 mg once daily, was measured in double-blind, placebo-controlled studies of patients with seasonal allergic rhinitis. These studies also demonstrate statistically significant benefit from the study drugs compared with placebo in relieving all nasal symptoms except congestion. Both drugs also relieved ocular pruritus. Fewer studies have assessed azelastine, acrivastine, and loratadine, but all have been shown to provide significant relief of seasonal allergic rhinitis compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind comparison of levocabastine nasal spray with sodium cromoglycate nasal spray in the treatment of seasonal allergic rhinitis.

Nasal levocabastine (0.5 mg/mL) was evaluated for efficacy and tolerance against sodium cromoglycate (20 mg/mL) in a 2-week double-blind trial in 27 and 29 patients with seasonal allergic rhinitis. Globally at 2 weeks, the investigators found a 74% response rate in the levocabastine patients versus a 50% response rate in the cromoglycate patients (P less than .10). Sneezing responded better to levocabastine than to cromoglycate according to three efficacy indicators derived from patient diary ratings of symptom severity: sum of severity scores over the total treatment period as a percentage of the theoretical maximum sum of severity scores (median: 19% versus 41%, P = .01); percentage of symptom-free days (median: 46% versus 22%, P less than .07); percentage of days with moderate or severe symptoms (median: 0% versus 29%, P = .004). Further, the percentage of days with moderate or severe runny nose was lower than in cromoglycate patients (median: 0% versus 25%, P = .09). Although no significant differences were found for itchy nose, blocked nose, and ocular symptoms, severities tended to be generally less under levocabastine than under sodium cromoglycate. Adverse experiences were low level and of similar incidence in the two groups. It is concluded that in a q.i.d. schedule, levocabastine nasal spray is more efficacious than sodium cromoglycate in relieving sneezing and that it is equally well tolerated.

Multicenter, crossover study of the efficacy and tolerability of terfenadine, 120 mg, versus cetirizine, 10 mg, in perennial allergic rhinitis.

In this 3-week randomized, double-blind, double-dummy multicenter, crossover study terfenadine, 120 mg, was compared with cetirizine, 10 mg, both given once daily in the treatment of perennial allergic rhinitis in sixty patients. Compared with the investigators' pretreatment assessment, both terfenadine and cetirizine significantly reduced the severity of all five symptoms (P less than .001). The two treatments were equally effective in controlling eye irritation, sneezing, nasal congestion and itchy nose, throat and palate, but cetirizine improved rhinorrhea more than terfenadine (P less than .05). Daily symptom assessments by the patients for the last 14 days of each treatment period showed no difference in efficacy between the two drugs for any of the symptoms. There were also no differences between the two drugs for overall assessments of efficacy or patient preference. Adverse events were recorded more frequently while taking cetirizine, with 14 attributable events compared with only five with terfenadine. Four of the cetirizine-related events were drowsiness or tiredness, but none was reported while patients were taking terfenadine. There was a tendency to increased weight (greater than 1 kg) with both treatments.

Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.

The efficacy of astemizole, diphenhydramine, and hydroxyzine hydrochloride in the treatment of chronic idiopathic urticaria was evaluated in this 3-month double-blind, randomized, parallel group study. Thirty-six adult patients were randomly assigned, 13 to the astemizole group (10 mg daily), 12 to the diphenhydramine group (25 mg t.i.d.), and 11 to the hydroxyzine hydrochloride group (25 mg t.i.d.). Demographic data were statistically similar for all variables assessed in the three treatment groups. Seven (58%) of the diphenhydramine patients withdrew before the end of the study, six because of lack of efficacy and one because of drowsiness. Two (18%) of the hydroxyzine hydrochloride patients withdrew, one because of lack of efficacy and one because of drowsiness. Two patients (15%) in the astemizole group withdrew, one because of adverse reaction, and the other because of lack of efficacy. Mean total symptom scores and mean individual symptom scores were lower in the astemizole group than in the other two groups. Wheal area measurements (0.1 mg/mL histamine challenge) decreased more in the astemizole and hydroxyzine hydrochloride groups than in the diphenhydramie group (P = .02). With regard to symptoms, 12/13 patients in the astemizole group improved clinically during their treatment period, versus 8/11 in the hydroxyzine hydrochloride group and 5/12 in the diphenhydramine group. The mean time to first observed therapeutic effect (maintained for three consecutive days) was 5.5 days in the astemizole group, 10.9 days in the hydroxyzine hydrochloride group, and 7.2 days in the diphenhydramine group. In this study, astemizole was as effective as hydroxyzine in patients treated for chronic idiopathic urticaria.

Double-blind comparison of cetirizine and placebo in the treatment of seasonal rhinitis.

The efficacy and safety of cetirizine were evaluated in 419 patients with seasonal allergic rhinitis. Using a 4-way, double-blind randomization schedule, patients were given a 1-week course of once daily cetirizine (5, 10, or 20 mg) or placebo. Patient and physician efficacy ratings corresponded, indicating superiority of cetirizine to placebo (P less than .05) in reducing symptom severity scores for sneezing, rhinorrhea, ocular pruritus, nasal pruritus, watering of the eyes, and redness of the eyes. All cetirizine doses achieved higher efficacy ratings (72.7%, 79.2%, and 75.7%, respectively) than placebo (52.9%; P less than .05) by the physician's global assessment. Cetirizine was well tolerated, with sedation being the most common adverse experience, increasing in frequency at higher doses. A dose-response relationship was evident for selected symptoms, and the once daily 5-mg dose was found to be an effective minimum dose.

Once versus twice daily dosing of terfenadine in the treatment of seasonal allergic rhinitis: US and European studies.

Terfenadine was compared for efficacy in treatment regimens of 120 mg once daily (qd) and 60 mg twice daily (bid) in patients with seasonal allergic rhinitis in double blind, randomized, parallel 1-week studies, three in Europe (one multicenter study, three sites; n = 191) and one in the US (single center; n = 201). Patients had moderate or severe symptoms for 2 or more years and positive skin tests to relevant pollen antigens. On entry and final visit individual symptoms were rated by physicians on a visual analog scale in Europe and a numerical scale in the US. Most patients filled out daily symptom diaries during the studies. Individual symptom scores and total symptom scores, (calculated by adding individual symptom scores together) as assessed by physicians and patients, were similar at baseline for both treatment regimens on entry, with improvement during the week. There were more patients with complete and marked relief in Europe than in the US. (Total symptom scores as assessed by physicians, for instance, improved from baseline ratings of 407 for the 60 bid regimen and 431 for the 120 qd regimen in Europe to 102 and 95 at final visit, and in the US from 8.8 for 60 bid and 8.5 for the 120 qd to 4.5 and 4.1). There was no statistical difference between the two treatment regimens in Europe or the US. Terfenadine, 120 mg once daily, is as effective as the currently approved dosage of 60 mg twice daily in the treatment of seasonal allergic rhinitis, and terfenadine, 120 mg once daily, has the added convenience of allowing the patient once a day dosing.