loratadine, Claritin
Protection against histamine-induced bronchoconstriction by loratadine.

Debelic M.

Clinic for lung diseases, asthma and allergy Auguste-Viktoria- und Cecilienstift, Bad Lippspringe, Germany.

In a simple blind pilot study we have examined the protective effect of loratadine, a new H1 histamine receptor antagonist, against bronchoconstriction induced by histamine inhalation. Six patients with an episodic or continuing obstructive bronchial disease and proven bronchial hyperreactivity were submitted to two identical histamine challenges, first without premedication and then after three days' treatment with 10 mg loratadine daily. The mean FEV1 fall in the first test after histamine inhalation was 33% and in the second test after pretreatment with loratadine only 3.3% (p less than 0.01). Five out of six patients have shown complete protection against histamine-induced bronchoconstriction, in one patient the protection was partial. We conclude that loratadine effectively inhibits histamine-induced bronchoconstriction and could be useful in the prophylactic treatment of asthma and obstructive bronchitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1357946&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Studies of nonsedative antihistamines. II. Assessment of its antihistaminic potency.

Aparicio S, Granel C, Randazzo L, Valencia M, Olive Perez A.

Hospital de la Santa Creu i Sant Pau, Unitat d'Al.lergia, Barcelona.

An analysis is made of the effectiveness of terfenadine at dosages of 60 and 120 mg, of cetirizine at a dose of 10 mg, and of loratadine and ebastine at a dose of 10 mg in inhibiting the papule induced by 20 mcg of intradermal histamine. Although all produced significant inhibition, cetirizine and terfenadine 120 mg showed a significantly greater inhibition coefficient than loratadine.

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loratadine, Claritin
Evaluation of loratadine as an inducer of liver microsomal cytochrome P450 in rats and mice.

Parkinson A, Clement RP, Casciano CN, Cayen MN.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.

The non-sedating anti-histamine, loratadine [ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin- 11-ylidene-1-piperidinecarboxylate], was administered orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 weeks. The effects of these treatments on liver microsomal cytochrome P450 were evaluated by immunochemical and biochemical techniques, and were compared with the effects of treating rats with three different inducers of cytochrome P450, namely phenobarbital, 3-methylcholanthrene and dexamethasone. Treatment of rats with loratadine caused a dose-dependent increase in the levels of P450 2B1 and 2B2, the major phenobarbital-inducible P450 enzymes, as determined by Western immunoblotting. At the highest dosage tested, loratadine was less effective than phenobarbital as an inducer of 2B1 and 2B2, although the induction of these proteins could be detected immunochemically even at the lowest dosage of loratadine tested. Consistent with these observations, treatment of rats with loratadine caused a dose-dependent increase in the rate of two reactions that are catalyzed predominantly by 2B1/2, namely testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation. At the highest dosage tested, loratadine caused a 7.3- and 8.5-fold increase in the rate of testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation, respectively, compared with a 22- and 45-fold increase caused by phenobarbital treatment. Treatment of rats with loratadine caused a 1.4- to 2.0-fold increase in the 2 beta-, 6 beta- and 15 beta-hydroxylation of testosterone, which was associated with a similar increase in the levels of immunoreactive P450 3A1 and/or 3A2. As an inducer of P450 3A1/2, loratadine was slightly less effective than phenobarbital, and was considerably less effective than dexamethasone, which caused a 10- to 33-fold increase in testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activity. At the dosages tested, loratadine did not increase the levels of P450 1A1, the major 3-methylcholanthrene-inducible P450 enzyme, as determined by Western immunoblotting. The rate of 7-ethoxyresorufin O-dealkylation, which is catalyzed predominantly by P450 1A1, increased 1.9-fold after loratidine treatment, but this increase was less than that caused by phenobarbital treatment (2.2-fold), and was considerably less than that caused by 3-methylcholanthrene treatment (33-fold). The effects of treating mature male mice with loratadine on liver microsomal cytochrome P450 resembled the effects observed in rats. These results indicate that loratadine is a phenobarbital-type inducer of liver microsomal cytochrome P450 in rats and mice.

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

Simpson K, Jarvis B.

Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail adis.co.nz

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.

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loratadine, Claritin
Treatment of urticaria and angioedema: low-sedating H1-type antihistamines.

Soter NA.

Department of Dermatology, New York University School of Medicine, Charles C. Harris Skin and Cancer Pavilion, New York University Medical Center 10016.

H1-type antihistamines are considered the therapeutic agents of choice for treating urticaria and angioedema. The use of traditional H1 antihistamines is limited by their side effects. In recent years low-sedating H1 antihistamines with reduced sedative and anticholinergic side effects have become popular choices for the treatment of urticaria and angioedema. Terfenadine and astemizole are currently available in the United States, and cetirizine and loratadine, currently under review at the Food and Drug Administration, are available in other countries. Terfenadine, cetirizine, and loratadine achieve rapid peak plasma concentrations in 1 to 2 hours, whereas astemizole has a slow onset of action. In double-blind, placebo-controlled studies of chronic idiopathic urticaria, low-sedating H1 antihistamines were more effective than placebo. The choice of a particular low-sedating H1 antihistamine depends on pharmacokinetic considerations and frequency of administration.

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loratadine, Claritin
[Non-sedative antihistaminics and binding to central and peripheral H1 histamine receptors]

[Article in French]

Leysen JE, Gommeren W, Janssen PF, Sanz G, Gillardin JM, Schotte A, Janssen PA.

Janssen Research Foundation, Beerse, Belgique.

Four non-sedating antihistamines (astemizole, cetirizine, loratadine and terfenadine) were investigated for in vitro and ex vivo binding to histamine-H1 receptors in guinea-pig cerebellum and lung. In vitro, all the drugs dissociated slowly from H1 receptors (half-times greater than or equal to 100 min), Ki,app-values decreased with longer incubation times for potent lipophylic agents (astemizole and terfenadine) Ki,app-values were lower with more dilute tissue suspensions. In optimized assay conditions astemizole showed a Ki,app-value of 0.2 microM. Terfenadine, cetirizine and loratadine bound with 30-, 80- and 100-times lower affinity to H1 receptors. The occupancy of lung and cerebellar H1 receptors was investigated after oral administration of various dosages of the drugs and at several times after drug administration, using ex vivo binding techniques. Astemizole was a very potent compound showing complete differentiation between lung and cerebellar receptor occupation (with 0.63 mg/kg: 70% of lung H1 receptors were occupied, with less than 10% of cerebellar H1 receptor occupancy). A 7-times higher dose of terfenadine was required to induce the same effect. Astemizole produced a rapid and complete occupancy of lung receptors, which was maintained up to 72 h after administration. In contrast, terfenadine produced a peak effect at 1 h and was completely eliminated from lung receptors in 24 h. Loratadine and cetirizine only poorly differentiated between lung and cerebellar receptor occupancy (at 2.5 mg/kg: 70 and 60% of lung receptor occupancy, 50 and 70% of cerebellar receptor occupancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1677249&dopt=Abstract loratadine, Claritin